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Investigational Therapeutic KW-0761 Efficiently Depletes Immune System–suppressing Treg Cells204082410/1/2015 12:19:56 PM Releases/AllItems.aspx766False2015-10-01T04:05:00Z<div class="ExternalClass7565F5E214814F1298EF66CC472537FE"><p>PHILADELPHIA — Immune cells called Tregs, which can inhibit anticancer immune responses, were efficiently eliminated from the blood of patients with lung or esophageal cancer by treatment with the investigational therapeutic antibody KW-0761, according to results of a phase Ia <a href="http&#58;//" target="_blank">clinical trial published</a> in <em>Clinical Cancer Research</em>, a journal of the American Association for Cancer Research.<img alt="Ryuzo Ueda, MD, PhD" src="/PublishingImages/Ueda_Ryuzo_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" /></p><p>“Tregs, which are characterized by expression of the proteins FoxP3 and CD4, have several important roles in the immune system, one of which is to prevent the immune system from attacking the body and causing autoimmune diseases,” said Ryuzo Ueda, MD, PhD <em>(right)</em>, professor in the Department of Tumor Immunology at Aichi Medical College in Nagoya, Japan. “However, they also suppress the immune response against cancer.</p><p>“Our hypothesis was that depleting Tregs in patients with cancer may augment the natural anticancer immune response,” continued Ueda. “Because activated FoxP3+CD4+ Tregs that accumulate in tumor tissue have been shown to express CCR4 molecules on their surface, we used the CCR4-targeted antibody KW-0761 to deplete Tregs in patients with lung or esophageal cancer.”<img alt="Eiichi Nakayama, MD, PhD" src="/PublishingImages/Nakayama_Eiichi_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" /></p><p>“We were pleased to see that infusion of even a small amount of the KW-0761 efficiently depleted Tregs from the peripheral blood for a long time [several months],” said the co-senior author on the study, Eiichi Nakayama, MD, PhD <em>(right)</em>, a professor at Kawasaki University of Medical Welfare in Kurashiki, Japan. “Unfortunately, we observed only a modest induction of antitumor immune responses and no marked clinical responses with KW-0761 monotherapy. Thus, we are planning to investigate whether combining Treg depletion with other immunotherapies, such as checkpoint inhibitors, can augment the antitumor immune response in patients with cancer.”</p><p>Ueda, Nakayama, and colleagues enrolled seven patients with non–small cell cancer and three patients with esophageal cancer in the phase Ia clinical trial. Patients were assigned to receive either 0.1, 0.5, or 1.0 mg of KW-0761 per kg of body weight weekly for eight weeks and then monthly until disease progression. Blood samples were obtained before the first treatment and then every four weeks, and then analyzed by flow cytometry to determine numbers of different immune cells.</p><p>The researchers found that the number of FoxP3+CD4+ Tregs in the blood of all patients was dramatically reduced following treatment with KW-0761. Four patients had stable disease, as assessed by <a href="http&#58;//" target="_blank">RECIST 1.1</a> criteria.</p><p>There were no dose-limiting toxicities and most adverse events were grade 1 or grade 2, with skin-related adverse events occurring most frequently.</p><p>According to Ueda and Nakayama, major limitations of the study include that the data are from a small number of patients, that Treg levels were measured in blood and not in tumors, and that KW-0761 monotherapy led to only modest induction of antitumor immune responses and no marked clinical responses. Thus, the researchers say that further studies need to be conducted to determine whether KW-0761 monotherapy depletes Tregs in the tumor microenvironment and to gain further insight into the role of Tregs in the complex immune network controlling the antitumor immune response.</p><p>This study was funded by the Ministry of Health, Labour, and Welfare of Japan; the Ministry of Education, Culture, Sports, Science, and Technology of Japan; and the Japan Society for the Promotion of Science. KW-0761 was provided by Kyowa Hakko Kirin. Ueda receives a research grant from Kyowa Hakko Kirin and Nakayama declares no conflicts of interest.</p></div>
Stand Up To Cancer Canada – Canadian Breast Cancer Foundation Dream Team Is Announced, Just One Year after Inaugural Telecast20850789/30/2015 6:59:12 PM Releases/AllItems.aspx768False2015-09-30T14:00:00ZCA$9 million investment will support groundbreaking research and treatments through new, collaborative, pan-Canadian team led by Tak W. Mak and Samuel Aparicio <div class="ExternalClass35936B17C6E5408A894898BFDF155423"><p>​TORONTO — A Stand Up To Cancer Canada Dream Team researching new approaches to treating triple-negative breast cancer (TNBC) and other aggressive types of breast cancer has been formed thanks to a CA$9 million investment from a coalition of funders.<br></p><p>The Dream Team reflects a collaboration of Stand Up To Cancer Canada (SU2C Canada), the Canadian Breast Cancer Foundation (CBCF), with support from CIBC and the Ontario Institute for Cancer Research (OICR). The American Association for Cancer Research (AACR) International – Canada, is SU2C Canada’s scientific partner.<br></p><p>Tak W. Mak, PhD, director of the Campbell Family Institute for Breast Cancer Research at Princess Margaret Cancer Centre in Toronto, is leader of the Dream Team. The Dream Team co-leader is Samuel Aparicio, BM, BCh, PhD, Nan and Lorraine Robertson chair in breast cancer research at the University of British Columbia in Vancouver and head of the Department of Breast and Molecular Oncology at the BC Cancer Agency. &#160;<br></p><p>The SU2C Canada-CBCF Breast Cancer Dream Team is the first to be announced since SU2C Canada was launched in 2014. The team is funded over a period of four years for CA$6 million provided by SU2C and by CBCF, with support from CIBC, and CA$3 million from OICR. The team will conduct clinical trials in six provinces, with those in Ontario funded by the OICR commitment. SU2C Canada funds derive from its nationwide telecast last year that appealed to the Canadian public to pledge support for cancer research, awareness, and education. <br></p><p>The Dream Team’s research project seeks to develop new therapies for aggressive breast cancers. These novel treatments will be aimed at changes in the genomes of cancer cells that make the tumours unstable and vulnerable to attack. That is, these new drugs will exploit the cancer’s “Achilles’ heel.” The Dream Team will test three candidate drugs for their effectiveness in halting or slowing the processes by which cancer cells reproduce. The researchers also hope to identify biomarkers of drug activity that will help match patients with the most effective treatments for their particular form of breast cancer.<br></p><p>“Attacking the genetic instability of the tumour cells in aggressive breast cancers hasn’t really been tried before,” Mak said. “We will give our new drugs to patients for whom other treatments have not worked, and monitor them to see whether a significant percentage of these patients responds to one or more of these drugs. By respond, we mean that we hope these patients’ tumours shrink, or at least that their disease holds steady rather than getting worse.” <br></p><p>“If our clinical trials are successful, our program has the potential to eventually deliver new drugs that will act against several very aggressive breast cancer subtypes, which currently lack effective targeted therapies,” Aparicio said. “By exploiting our increased understanding of cancer evolution and genomics to the single-cell level, we hope to co-develop biomarkers and treatment combination strategies that will identify the patient groups most likely to benefit from the new drugs we are testing.”<br></p><p>In addition to the leaders, the principal investigators on the Dream Team include Morag Park, PhD, director, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal; Kathleen Pritchard, MD, senior scientist at Sunnybrook Research Institute, University of Toronto; and Karen Gelmon, MD, professor of medicine at the University of British Columbia in Vancouver. </p><p>Serving as advocates for patients, their loved ones, and those at risk are Randy Mellon of Toronto, breast cancer survivor and patient advocate; Zuri Scrivens of Langley, British Columbia, breast cancer survivor and patient advocate; and Wendie den Brok, MD, advanced TNBC survivor and medical oncologist in training at the BC Cancer Agency in Vancouver. Den Brok will also serve as an investigator on the scientific team.<br></p><p>“We lack effective treatments for TNBC and other types of aggressive breast cancer,” said Phillip A. Sharp, PhD, Nobel laureate and institute professor at the Massachusetts Institute of Technology’s David H. Koch Institute for Integrative Cancer Research, who serves as co-chair of the SU2C Canada Scientific Advisory Committee (CSAC). “The SU2C Canada-CBCF Breast Cancer Dream Team plans to change this by developing new drugs that will target the vulnerabilities of this disease.”<br></p><p>Serving with Sharp as co-chair of the CSAC is Alan Bernstein, PhD, president and chief executive officer of the Canadian Institute for Advanced Research (CIFAR). <br></p><p>“The new Dream Team is made up of some of Canada’s top cancer researchers, building on many years of outstanding research conducted in Canada,” Bernstein said. “Importantly, the clinical trials will be carried out across the country. This is Canadian science at its best.” <br></p><p>Dramatic advances in breast cancer therapy in recent years have led to fewer women dying from the disease, noted Lynne Hudson, CEO of CBCF. <br></p><p>“But one in nine women in her lifetime can expect to be diagnosed with breast cancer, and we need to do better,” Hudson said. “Developing new therapies that get to patients faster, particularly for subtypes that don’t have the same kind of treatment options as the more common types of breast cancer, is a priority for us and our community. This partnership with SU2C Canada – and most significantly this Dream Team – is really about boldly pushing into those new areas and developing desperately needed treatments.”<br>“With so many Canadian families affected by breast cancer, CIBC is proud to continue our longtime partnership with the Canadian Breast Cancer Foundation by supporting this outstanding Dream Team,” said Christina Kramer, CIBC executive vice president, and its Executive Run Sponsor for the CIBC Run for the Cure. “By investing in innovative collaborations like this, we will change the future of breast cancer here in Canada and around the world.”<br></p><p>OICR’s funding will be critical in setting up early clinical trials to test the new drugs, once their safety and effectiveness has been shown in the laboratory according to Thomas J. Hudson, MD, president and scientific director of OICR. <br></p><p>“OICR and SU2C Canada share a common purpose in supporting translational research,” said Hudson. “That is, ensuring the best scientific discoveries in cancer research are successfully developed into new approaches and therapeutics that will benefit patients. We are happy to join forces with SU2C Canada and CBCF to support this team.”<br></p><p>“Ontario is pleased to support innovative research through the Ontario Institute for Cancer Research,” said Reza Moridi, Ontario Minister of Research and Innovation. “This Dream Team is a perfect example of the type of collaboration that our province is looking to foster and promote. Finding new and innovative ways to treat breast cancer brings hope to patients and their families and has the potential to create major health and economic benefits.”<br>The SU2C Canada-CBCF Breast Cancer Dream Team is one of the two inaugural Dream Teams evaluated by the CSAC. SU2C Canada, a project of EIF Canada, a Canadian registered charity, also plans to announce the second Dream Team, which is focused on cancer stem cells.<br></p><p>The Mak-Aparicio team was selected after careful consideration by the CSAC led by Sharp and Bernstein. The review process began with a Call for Ideas issued by AACR International – Canada in October 2014. Three finalist teams met with the CSAC and the Breast Cancer Subcommittee in Toronto in June 2015 to present their plans and respond to questions, an unusual level of face-to-face interaction between applicants and reviewers that helps to ensure that the best applicant is selected. <br></p><p>In addition to Sharp and Bernstein, the CSAC consists of Carlos L. Arteaga, MD, professor of medicine and cancer biology at Vanderbilt University School of Medicine in Nashville, Tennessee; Carol L. Prives, PhD, DaCosta professor of biological sciences at Columbia University in New York; Jenny C. Chang, MD, Emily Herrmann chair in cancer research and director of the Cancer Center at Houston Methodist Hospital in Houston; and Sheila Toews, former chair of the Manitoba Provincial Health Ethics Network, as patient advocate. Also involved in the review was the CSAC Breast Cancer Subcommittee, chaired by Nancy E. Davidson, MD, director of the University of Pittsburgh Cancer Institute; Shannon L. Puhalla, MD, assistant professor, University of Pittsburgh School of Medicine; Laura J. van ’t Veer, PhD, professor at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center; and Eric P. Winer, MD, chief of women’s cancers at the Dana-Farber Cancer Institute in Boston.<br></p><p>As the scientific partner to SU2C Canada, the AACR International – Canada, the Canadian arm of the world’s largest scientific organization devoted to cancer research, is responsible for administering the research agreement and providing oversight to ensure that progress is being made. <br><br></p></div>
American Association for Cancer Research Launches June L. Biedler Prize for Cancer Journalism20710169/28/2015 7:32:23 PM Releases/AllItems.aspx767False2015-09-28T19:40:00ZCall for Entries Now Open; Robert Bazell Chairs Judging Panel<div class="ExternalClass927BCF8921CB4B49A07ADCEB154904F4"><p>​PHILADELPHIA — The American Association for Cancer Research (AACR) announces the call for entries for the inaugural June L. Biedler Prize for Cancer Journalism to raise awareness of the critical role the media play in educating the public about cancer and cancer research. The deadline for submission is Monday, Jan. 11, 2016. The judging panel will be chaired by Robert Bazell, adjunct professor of molecular, cellular, and developmental biology at Yale University and former chief science and health correspondent for NBC News.</p><p>The AACR Biedler Prize is named in honor of June L. Biedler, PhD, a visionary cancer scientist and mentor who was dedicated to furthering science and health care communications. Biedler was a former member of the board of directors of the AACR and recipient of the 1992 AACR G.H.A. Clowes Memorial Award, which honors outstanding achievement in basic cancer research. The new AACR award in Biedler's name recognizes and rewards journalists who have produced accurate, informative, and compelling stories about cancer, cancer research, and cancer policy with a $5,000 cash award.</p><p>&quot;Dr. Biedler was an inspirational woman, a pioneer in cancer research who held a strong belief that communication is critical to accelerating the pace of progress against cancer,&quot; said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. &quot;She cared deeply about the mission of the American Association for Cancer Research (AACR) and its efforts to educate the public about science and the importance of cancer research for public health. Therefore, it is with great pride that the AACR has established the June L. Biedler Prize for Cancer Journalism to recognize outstanding journalistic coverage that enhances the public's understanding of cancer and cancer research.&quot;</p><p>The AACR Biedler Prize is open to print, broadcast, and online professional journalists whose stories appear in media that target a lay public audience. The AACR Biedler Prize consists of six submission categories&#58; large newspaper (circulation over 100,000); small newspaper (circulation under 100,000); magazine; online/multimedia; television; and radio.</p><p>The AACR Biedler Prize will be presented during the AACR Annual Meeting, April 16-20, 2016, in New Orleans.</p><p>For more information or to submit a story to be considered for the AACR June L. Biedler Prize for Cancer Journalism, go to <a href="/Newsroom/Pages/aacr-june-biedler-prize-for-cancer-journalism.aspx"></a>.</p></div>
Robert D. Schreiber, PhD, and Philip D. Greenberg, MD, Named New Editors-in-chief of AACR Journal Cancer Immunology Research20357979/24/2015 1:31:02 PM Releases/AllItems.aspx765False2015-09-24T13:30:00Z<div class="ExternalClass2C39AE5E08314F3FA81628C7E12CD7A4"><p>PHILADELPHIA — The American Association for Cancer Research (AACR) recently announced the appointment of Robert D. Schreiber, PhD, and Philip D. Greenberg, MD, as editors-in-chief of <a href="http&#58;//" target="_blank"><em>Cancer Immunology Research</em></a>, one of eight peer-reviewed journals published by the AACR. In their roles, Schreiber and Greenberg will set goals and determine editorial strategy for the journal.&#160;&#160; </p><p><em>Cancer Immunology Research</em> publishes original articles reporting advances in cancer immunology and immunotherapies that span the spectrum of science and medicine, from basic investigations in host-tumor interactions to developmental therapeutics in model systems, early translational studies in patients, and late-stage clinical trials. The journal disseminates the latest developments in the field to cancer researchers in all disciplines, catalyzing the cross-disciplinary work needed to yield improved clinical outcomes. </p><p>“We are honored and excited about the opportunity to lead <em>Cancer Immunology Research</em>. Together with my co-editor-in-chief, we hope to establish the journal as the definitive voice in this rapidly expanding field,” said Schreiber. </p><p>“<em>Cancer Immunology Research</em> has as its goal becoming the publication forum for the breadth of investigators and clinicians engaged in or interested in immunology, particularly as it relates to cancer,” added Greenberg. </p><p>“In 2013, the AACR launched <em>Cancer Immunology Research</em> with Glenn Dranoff as the founding editor-in-chief to capture the most significant work in the field of cancer immunology and to highlight the relationship of cancer immunology to other areas of cancer research,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “The AACR owes much gratitude to Dr. Dranoff for his editorial vision and for the journal’s many early successes. Under the new leadership of Drs. Schreiber and Greenberg, the journal will continue its commitment to publish all aspects of cancer immunology and immunotherapy.”</p><p>Schreiber is the alumni endowed professor of pathology and immunology and director of the Center for Human Immunology and Immunotherapy Programs at Washington University School of Medicine in St. Louis. His earlier work focused on the interaction of the immune system with developing cancers and led to elucidation of the process known as cancer immunoediting. </p><p>Recently, Schreiber and colleagues used genomics approaches to identify somatic mutations in tumors that give rise to tumor-specific mutant antigens and showed that some tumor neoantigens are targets of T cells that respond to immune checkpoint antibodies. He further showed that tumor-specific neoantigens can form the basis for therapeutically effective personalized cancer vaccines.</p><p>Schreiber has received many honors, including the William B. Coley Award from the Cancer Research Institute (CRI), the Charles Rodolphe Brupbacher Prize for Cancer Research, and the AACR-CRI Lloyd J. Old Award in Cancer Immunology. He is a member of the AACR, the American Academy of Arts and Sciences, and the U.S. National Academy of Sciences. He has been a member of numerous editorial boards, including <em>Cancer Immunology Research</em>. He received both his bachelor’s and doctoral degrees from the State University of New York at Buffalo.&#160; </p><p>Greenberg is a professor of medicine/oncology and immunology at the University of Washington and head of the Program in Immunology at the Fred Hutchinson Cancer Research Center in Seattle. His career has focused on elucidating fundamental principles underlying a T cell’s ability to recognize and eliminate tumor cells, to distinguish cancer cells from normal cells, and to maintain function in the tumor microenvironment. His lab is developing cellular and molecular approaches to manipulate cellular immunity and overcome obstacles to effective immunotherapy, and is translating laboratory studies to the treatment of cancer patients, with a particular emphasis on adoptive therapy with genetically engineered T cells. </p><p>Greenberg’s honors include the William B. Coley Award from CRI and the Team Science Award for Career Achievements from the Society for the Immunotherapy of Cancer, among many others. He is a member of the AACR, the American Society of Clinical Investigation, the Association of American Physicians, the American College of Physicians, and the American Association for the Advancement of Science. He has served on editorial boards of multiple publications, including <em>Cancer Immunology Research</em>. He received his bachelor’s degree from Washington University and his medical degree from the State University of New York, Downstate Medical Center.&#160; </p></div>
Pancreatic Cancer Action Network and American Association for Cancer Research Invite Applications for 2016 Research Grants19832419/18/2015 3:40:52 PM Releases/AllItems.aspx764False2015-09-18T15:40:00Z<div class="ExternalClass0F070726126249C3A69BF95A134A2335"><p>​PHILADELPHIA — The American Association for Cancer Research (AACR) and the <a href="http&#58;//" target="_blank">Pancreatic Cancer Action Network</a> are pleased to announce the opening of the 2016 <a href="/Funding/Pages/2016-pancreatic-cancer-action-network-AACR-research-grants-program.aspx" target="_blank">Research Grants Program</a> to support early-career investigators to focus on pancreatic cancer.</p><p>Two grant mechanisms, the Pathway to Leadership Grant and the Career Development Award, are being offered for postdoctoral or clinical research fellows or junior independent researchers, respectively.</p><p>&quot;Pancreatic cancer is among the most deadly of cancers,&quot; said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. &quot;With death rates anticipated to rise over the coming decades, additional research in pancreatic cancer is urgently required. The AACR is pleased to continue its partnership with the Pancreatic Cancer Action Network to provide grant opportunities to support innovative research projects that will accelerate the pace of progress against this devastating disease.&quot;</p><p>Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2030, according to <a href="/Newsroom/Pages/News-Release-Detail.aspx?ItemID=541" target="_blank">research</a> conducted by the Pancreatic Cancer Action Network and published in <em>Cancer Research</em>, a journal of the AACR.</p><p>&quot;We are thrilled to partner with organizations like the AACR as we continue to recruit the brightest scientists and build a broad research community,&quot; said Julie Fleshman, president and chief executive officer of the Pancreatic Cancer Action Network. &quot;Our grant recipients have been shaping the research field and are actively bringing us closer to improving patient outcomes.&quot;</p><p>Since the Pancreatic Cancer Action Network–AACR grants program was introduced in 2003, more than $27 million has been awarded to accelerate pancreatic cancer research. This year, $1.2 million will be available through this partnership to support the nation's most promising early-career scientists in the field.</p><p>Submissions for 2016 grants must be completed online using the <a href="https&#58;//" target="_blank">proposalCENTRAL website</a>. Funding decisions will be announced in the spring and the grant term will begin July 1, 2016. The recipients will be honored at the <a href="/Meetings/Pages/MeetingDetail.aspx?EventItemID=63" target="_blank">AACR Annual Meeting 2016</a>, held in New Orleans, April 16-20. Please see below for grant deadlines.</p><p><strong>Career Development Awards</strong><br> <a href="/Funding/Pages/Funding-Detail.aspx?ItemID=26" target="_blank">Career Development Awards</a> are two-year grants totaling $200,000 to support junior independent investigators in developing or strengthening their research programs in pancreatic cancer.</p><p>The letter of intent deadline is noon ET, Oct. 8, 2015.</p><p><strong>Pathway to Leadership Grant </strong><br>The <a href="/Funding/Pages/Funding-Detail.aspx?ItemID=23" target="_blank">Pathway to Leadership Grant</a> is a five-year grant totaling $600,000 that is designed to build future leadership in the pancreatic cancer research community by supporting a highly promising postdoctoral or clinical research fellow during his or her mentored research, continuing through his or her early phase of independence.</p><p>The application deadline is noon ET, Oct. 27, 2015.</p><p>To learn more about the 2016 grants program, visit <a href="/funding" target="_blank"></a> or <a href="http&#58;//" target="_blank"></a>.</p><p>Meet the past grant recipients and learn more about their funded projects <a href="https&#58;//" target="_blank">here</a>.</p></div>
Immune System–boosting Agent CpG-B Reduced Early-stage Melanoma Recurrences19555629/16/2015 12:56:34 PM Releases/AllItems.aspx758False2015-09-16T13:00:00Z<div class="ExternalClass7B9AFFA93340457FA6E039608E22A9D4"><p>​NEW YORK — Among patients with clinically stage 1 or stage 2 <a href="https&#58;//" target="_blank">melanoma</a>, those treated with the immune system–boosting agent CpG-B were less likely to experience recurrence of their disease than those who received placebo, according to results from two randomized, placebo-controlled phase II clinical trials presented at the <a href="/Meetings/Pages/MeetingDetail.aspx?EventItemID=54" target="_blank">CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference</a>, held Sept. 16–19.</p><p><img alt="Tanja D. de Gruijl, PhD" src="/PublishingImages/DeGruijl_Tanja_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" />&quot;Even though stage 1 and stage 2 melanomas can be removed surgically, in a considerable proportion of patients cells from the tumor have already spread and eventually lead to tumor recurrence,&quot; said Tanja D. de Gruijl, PhD, professor and head of the immunotherapy lab in the Department of Medical Oncology at the <a href="http&#58;//" target="_blank">VU University Medical Center Cancer Center Amsterdam</a> in the Netherlands. &quot;We set out to investigate whether intradermal [within the skin] injection of the immune-stimulatory compound CpG-B around the site of surgical removal of the primary tumor could boost patients' antimelanoma immune responses and provide local and systemic protection against early metastatic events that could otherwise lead to tumor recurrence.</p><p>&quot;We found that there was a significant prolongation of recurrence-free survival among the patients who had received CpG-B compared with the patients who received saline placebo,&quot; continued de Gruijl. &quot;The apparent clinical effect was much stronger than we had anticipated and underlines the powerful ability of the immune system, provided it is properly activated, to control melanoma.&quot;</p><p>CpG-B is a reagent that closely resembles a stretch of bacterial DNA, explained de Gruijl. It is perceived by the human immune system as a sign of danger that calls for an immune response.</p><p>From 2004 to 2007, de Gruijl and colleagues enrolled 52 patients with clinically stage 1 or stage 2 melanoma in the two clinical trials. Patients were assigned intradermal injection of either CpG-B or saline. Injections were administered directly adjacent to the site of surgical excision of the primary melanoma tumor, seven and two days before re-excision and sentinel lymph node biopsy, which de Gruijl explained are part of the standard of care at VU University Medical Center Cancer Center Amsterdam.</p><p>The researchers found that after a median follow-up of 76.5 months, two of the 30 patients assigned CpG-B and nine of the 22 patients assigned placebo had experienced melanoma recurrence.</p><p>&quot;Our results imply that local conditioning of the melanoma excision site by simple intradermal administration of an immune-stimulatory compound like CpG-B can lead to boosting of a systemic antimelanoma immune response that affords protection against recurrences in the long term, with minimal transient side effects,&quot; said de Gruijl. &quot;We plan to conduct a large, randomized phase III clinical trial of intradermal CpG-B versus saline to confirm our findings of prolonged long-term recurrence-free survival.&quot;</p><p>According to de Gruijl, the major limitations of the study are that the data are the combined results of two phase II clinical trials with low numbers of enrolled patients and that different CpG-B doses were used in the two clinical trials. The low patient numbers mean that a large, randomized phase III clinical trial is needed to confirm the current promising findings, she added.</p><p>This study was supported by funds from the Fritz Ahlqvist Foundation. Pfizer provided the CpG-B for the clinical trial. De Gruijl declares no conflicts of interest.</p><p><img src="/PublishingImages/Twitter-bird-blue-on-white_50x50.jpg" alt="" style="margin&#58;5px 10px;" />Follow the meeting on Twitter&#58; <a href="https&#58;//" target="_blank">#cicon15</a></p></div>
Frequency of Certain Immune Cells in Blood May Predict Metastatic Melanoma Response to Pembrolizumab19556059/16/2015 12:55:19 PM Releases/AllItems.aspx759False2015-09-16T13:00:00Z<div class="ExternalClass34660D99A9ED4608817ACFF686BBA3D5"><p>​NEW YORK — Among patients with metastatic <a href="https&#58;//" target="_blank">melanoma</a> treated with the immunotherapy drug pembrolizumab (Keytruda), those whose cancer responded to the treatment had a higher frequency of immune cells called T cells that were positive for the proteins CD8, PD-1, and Bim (CD8+PD-1+Bim+ T cells) in blood samples taken immediately before starting pembrolizumab than those who had disease progression, according to data presented at the <a href="/Meetings/Pages/MeetingDetail.aspx?EventItemID=54" target="_blank">CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference</a>, held Sept. 16–19.</p><p><img alt="Roxana S. Dronca, MD" src="/PublishingImages/Dronca_Roxana_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" />Pembrolizumab, which targets the protein PD-1, was approved by the U.S. Food and Drug Administration for treating metastatic melanoma in September 2014. Some patients with metastatic melanoma have remarkable responses to pembrolizumab, whereas others do not respond at all, according to <a href="http&#58;//" target="_blank">Roxana S. Dronca, MD</a>, a medical oncology consultant and assistant professor of oncology at the Mayo Clinic in Rochester, Minnesota.</p><p>&quot;The discovery of a biomarker predictive of response to pembrolizumab would inform clinical decision-making,&quot; said Dronca. &quot;Not only would it help to identify those patients with metastatic melanoma, and possibly other malignancies, who are most likely to benefit from the immunotherapy, but it would also potentially help to identify those patients who are acquiring resistance to the agent during the course of treatment, thereby exposing fewer patients to inadequate treatments and their associated toxicities and costs.</p><p>&quot;Our results indicate that measuring the frequency of CD8+PD-1+Bim+ T cells in the peripheral blood of patients with metastatic melanoma may provide a way to predict or monitor responses to pembrolizumab,&quot; she added. &quot;A great advantage of the approach lies in the ease of serial peripheral blood testing compared with repeated invasive tissue biopsies. We are currently validating these results in a larger prospective cohort of patients with metastatic melanoma and lung cancer with multiple serial peripheral blood samples and standardized tumor assessment.&quot;</p><p>Dronca and colleagues analyzed a series of blood samples from 38 patients with metastatic melanoma using flow cytometry. For each patient, a blood sample was obtained immediately before starting pembrolizumab treatment. For 18 of the patients, further samples were obtained every 12 weeks at the time of tumor evaluation by radiographic imaging.</p><p>The researchers found that patients who experienced clinical benefit, as measured by <a href="http&#58;//" target="_blank">RECIST 1.1</a> complete response, partial response, or stable disease after four cycles of treatment had a higher frequency of CD8+PD-1+Bim+ T cells in the first blood sample at 12 weeks compared with patients with radiographic disease progression. The frequencies of these cells decreased significantly after the first 12 weeks of treatment in the blood of responders compared with nonresponders.</p><p>&quot;We previously showed that Bim is a downstream signaling molecule in the PD-1 signaling pathway and that levels of Bim reflect the degree of PD-1 interaction with its ligand PD-L1,&quot; said senior author Haidong Dong, MD, PhD, associate professor of immunology at the Mayo Clinic. &quot;We hypothesize that the increased frequency of CD8+PD-1+Bim+ T cells in responders reflects an increased number of target T cells for PD-1 blockade with pembrolizumab, which may explain the positive clinical outcomes in these patients.&quot;</p><p>According to Dronca, limitations of the study include the relatively small cohort of patients and the fact that only one version of anti-PD-1 antibody, pembrolizumab, was evaluated.</p><p>This study was supported by funds from the National Institutes of Health and the Cancer Research Institute. Dronca was the Mayo Clinic principal investigator on the pembrolizumab Expanded Access Program (EAP), on which most patients on this study were treated. With the approval of the sponsor, Merck Sharp &amp; Dohme Corp., the patients were offered participation in a distinct biomarker substudy, which was designed and led by Mayo Clinic. Dong is an inventor of technology related to this research.</p><p><img src="/PublishingImages/Twitter-bird-blue-on-white_50x50.jpg" alt="" style="margin&#58;5px 10px;" />Follow the meeting on Twitter&#58; <a href="https&#58;//" target="_blank">#cicon15</a></p></div>
Small Protein Engineered to Target PD-L1 is More Potent Than Anti-PD-L1 Antibody Immunotherapeutic19556999/16/2015 12:54:17 PM Releases/AllItems.aspx760False2015-09-16T13:00:00Z<div class="ExternalClassB30915E5212A41C096359E15E13AE76D"><p>​NEW YORK — An engineered high-affinity PD-1 small protein that can bind to PD-L1 on tumors was found to be a more effective anticancer immunotherapeutic than conventional anti-PD-L1 antibodies, and this small protein was more effective in synergizing with other immunotherapies compared with conventional anti-PD-L1 antibodies, according to preclinical data presented at the <a href="/Meetings/Pages/MeetingDetail.aspx?EventItemID=54" target="_blank">CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference</a>, held Sept. 16–19.</p><p><img alt="Sydney Gordon" src="/PublishingImages/Gordon_Sydney_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" />&quot;We now have many antibody drugs [such as pembrolizumab and ipilimumab] that target immune checkpoints such as PD-1, PD-L1, CTLA4, and other immune-regulatory pathways. However, these types of drugs have some overlooked drawbacks that can limit their effectiveness,&quot; said <a href="https&#58;//" target="_blank">Sydney Gordon</a>&#160;(<em>right</em>), a graduate student in the laboratory of <a href="https&#58;//" target="_blank">Irving Weissman, MD</a>, at the <a href="http&#58;//" target="_blank">Ludwig Center</a> at <a href="https&#58;//" target="_blank">Stanford University School of Medicine</a> in California.</p><p>&quot;First, it would be ideal if drugs that target PD-L1 could get inside tumors. However, antibodies, because of their large size, cannot get there effectively, which prevents them from working to their full potential,&quot; Gordon said. &quot;Second, antibodies against PD-1 and PD-L1 can result in counterproductive collateral damage, depleting some of the very antitumor immune cells they are supposed to activate.&quot;</p><p><img alt="Aaron Ring" src="/PublishingImages/Ring_Aaron_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" />Gordon; <a href="https&#58;//" target="_blank">Aaron Ring</a>&#160;(<em>rig</em><em>ht</em>), who is an MD/PhD student from Weissman's lab and will shortly be assistant professor in the Department of Immunobiology at Yale University School of Medicine; and colleagues hypothesized that a small engineered protein that targets PD-L1 and is capable of blocking PD-1/PD-L1 signaling could potentially overcome these setbacks and function as a superior immunotherapy.</p><p>The researchers designed a small-protein antagonist of PD-L1 by using a process called directed evolution. &quot;In the end, our best PD-1 variants bound to PD-L1 about 50,000 times more strongly than the natural PD-1 protein,&quot; Ring said. The small-protein, high-affinity PD-1 variant they developed was one-tenth the size of an antibody.</p><p>First, the researchers tested whether the high-affinity PD-1 protein could penetrate solid tissues more effectively than anti-PD-L1 antibodies. To do this, they labeled the high-affinity PD-1 protein and an anti-PD-L1 antibody with two differently colored fluorescent dyes and injected tumor-bearing mice with both fluorescent proteins at the same time. When they surgically removed the tumors and looked at them under a microscope, they found that the antibody was mostly found near blood vessels (outside the tumor), whereas the high-affinity PD-1 protein was able to distribute much more deeply into the tumors.</p><p>Next, the researchers tested what impact the high-affinity PD-1 protein had on immune cells. For this, they took blood samples and lymph nodes from mice treated with the PD-1 protein and those treated with the PD-L1 antibody, and estimated the number of T cells. They found that the high-affinity PD-1 protein did not affect T-cell numbers in the blood or lymph nodes, but the anti-PD-L1 antibody caused significant depletion of T cells. Further, they found that this depletion was worsened when they combined the antibody with other immunotherapies. &quot;This may have important implications when considering how to optimize immunotherapeutic combinations for patients,&quot; Gordon said.</p><p>Finally, they tested the antitumor activity of the high-affinity PD-1 protein and found that when mice had tumors about the size of a grain of rice (50 mm3), both PD-1 protein and anti-PD-L1 antibodies were effective in shrinking the tumors. However, when the mice had tumors about the size of a pea (150 mm3), the anti-PD-L1 antibodies were entirely ineffective, even when they were combined with anti-CTLA4 antibodies. The high-affinity PD-1 protein was able to slow the growth of big tumors, and it was more effective when combined with anti-CTLA4 antibodies.</p><p>&quot;Given how well anti-PD-1 and anti-PD-L1 antibodies are working for cancer patients, it may seem like a reasonable assumption that we have adequately targeted the pathway at this point. However, our results show that significantly more antitumor activity is possible using a small-protein therapeutic compared with a conventional antibody,&quot; Ring said. &quot;The broader implication is that small-protein therapeutics could present the same advantages in additional immunotherapeutic pathways outside of PD-1 and PD-L1.&quot;</p><p>Because of their small size, the high-affinity PD-1 proteins may get excreted from the body more quickly, which means that they would have to be administered more frequently than antibodies. Further, they may be &quot;immunogenic,&quot; meaning patients could develop an immune response to the drug itself. &quot;Both issues would need to be addressed for high-affinity PD-1 or a similar small-protein therapeutic to be developed for clinical use,&quot; Gordon said.</p><p>This study was funded by the Ludwig Center at Stanford. Several authors are inventors on a patent filing describing the high-affinity PD-1 agents. Sydney Gordon provides consulting services for Ab Initio Biotherapeutics. Several authors, including Aaron Ring, are founders of Ab Initio Biotherapeutics and serve on its scientific advisory board.</p><p><img src="/PublishingImages/Twitter-bird-blue-on-white_50x50.jpg" alt="" style="margin&#58;5px 10px;" />Follow the meeting on Twitter&#58; <a href="https&#58;//" target="_blank">#cicon15</a></p></div>
New Method of Immunotherapy Delivery Lowers Pain in Children With High-risk Neuroblastoma19561739/16/2015 12:50:51 PM Releases/AllItems.aspx763False2015-09-16T13:00:00Z<div class="ExternalClass4B98EB59DB794F6CA29FADBD0FA48CFB"><p>​NEW YORK — In children with high-risk relapsed/refractory neuroblastoma, long-term infusion (LTI) of the antibody ch14.18/CHO (dinutuximab-beta; the European counterpart of <a href="http&#58;//" target="_blank">dinutuximab</a>) in combination with other drugs lowered neuropathic pain, a major side effect encountered with the current standard mode of short-term infusion (STI) of the drug, according to data from a <a href="https&#58;//;rank=1" target="_blank">phase I/II clinical trial</a> presented at the <a href="/Meetings/Pages/MeetingDetail.aspx?EventItemID=54" target="_blank">CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference</a>, held Sept. 16–19.</p><p><img alt="Holger N. Lode, MD, PhD" src="/PublishingImages/Lode_Holger_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" />&quot;Neuroblastoma is a childhood cancer with one of the highest death rates,&quot; said Holger N. Lode, MD, PhD, professor and chair of pediatrics at University Medicine Greifswald in Germany. &quot;Treatment with an FDA-approved, neuroblastoma-specific monoclonal antibody, ch14.18, in combination with interleukin-2 and 13-cis-retinoic acid [13-cis-RA] has shown benefit for patients with this disease in the United States.</p><p>&quot;In Europe, ch14.18 was remanufactured using CHO cells commissioned by <a href="http&#58;//" target="_blank">SIOPEN</a>, funded by European charities, and further developed by Apeiron Biologics. Dinutuximab-beta was first evaluated for safety in a phase I study, which confirmed the tolerability and showed activity when given as STI with a dosing regimen of 20 mg/m2 given by eight-hour infusions on five consecutive days; however, it is associated with severe neuropathic pain,&quot; Lode said.</p><p>The ch14.18 antibody targets GD2, which is a molecule abundantly expressed on neuroblastoma with limited to no expression on most healthy tissues except nerve fibers that signal pain. As a result, treatment with ch14.18 antibody is associated with induction of neuropathic pain, a significant side effect in these patients, Lode explained.</p><p>&quot;A high amount of intravenous morphine is required to make STI tolerable for patients. Further, the rate of inflammatory side effects observed is substantial. We hypothesized that significant prolongation of the time of antibody infusion [LTI] will improve tolerability of the antibody while maintaining clinical activity and efficacy in high-risk neuroblastoma patients,&quot; Lode said.</p><p>&quot;In our study, by changing the method of antibody delivery from STI to LTI, we observed an impressive reduction of on-target [pain] and off-target [inflammation] side effects, while maintaining effective drug levels over the entire treatment period, as assessed in a variety of bioassays, demonstrating the immune-modulatory effect of ch14.18/CHO and its potency to mediate destruction of neuroblastoma cells constantly over a period of six months,&quot; Lode said.</p><p>In two clinical trials, an ongoing SIOPEN phase II study (APN311-202) and a closed single-center program (APN311-303), Lode and colleagues enrolled 44 patients and 53 patients, respectively, with high-risk relapsed/refractory neuroblastoma. Patients received a total dose of 100 mg/m2 of ch14.18/CHO per cycle given as LTI continuously over 10 consecutive days. Five cycles were given in five-week intervals, and all patients also received interleukin-2 and oral 13-cis-RA.</p><p>The investigators evaluated treatment-related pain by three-time daily assessment of validated age-adapted pain scoring systems by parents and/or the medical team, and daily use of intravenous morphine was recorded for each patient in each cycle. The investigators compared their observations of pain and adverse events from the LTI studies with the <a href="http&#58;//" target="_blank">previously published data</a> on neuroblastoma patients treated with STI of dinutuximab. Overall survival (OS) and progression-free survival (PFS) data from this study were compared with <a href="http&#58;//" target="_blank">previously reported</a> historical gold standard, which is a compilation of clinical trial data from comparable patients treated with modern-era front-line and relapse therapy.</p><p>Analysis of pain assessment scores and use of intravenous morphine indicated that LTI of ch14.18/CHO was associated with lowered pain, compared with data previously reported for children treated with STI. The investigators also observed lower frequencies of grade 3 or higher adverse events in the LTI group compared with the STI group, except for equal frequencies in vomiting, according to Lode.</p><p>After following the patients for a median of 2.9 years, one-year and four-year OS rates for patients treated with LTI in the SIOPEN cohort were about 94 percent and 61 percent, respectively, compared with about 56 percent and 14 percent, respectively, for those from the previous report.</p><p>After following the patients for a median of 2.8 years, one-year and four-year PFS rates for patients treated with LTI in the SIOPEN cohort were about 54 percent and 32 percent, respectively, compared with about 19 percent and 8 percent, respectively, for those from the previous report.</p><p>&quot;This is a big step forward for children with neuroblastoma,&quot; Lode said. &quot;The data provide an important baseline. They may have to be evaluated further in a randomized controlled clinical trial comparing STI and LTI.&quot; This would address the limitation of this study performed without a group treated with STI for direct comparison, Lode explained.</p><p>This study was funded by the cooperating group of pediatric oncologists of the SIOPEN-R-NET, Hector-Stiftung, University Medicine Greifswald, Deutsche Kinderkrebsstiftung, Polymun Scientific, Apeiron Biologics, and by charities from Europe. Lode is a consultant for Apeiron Biologics.</p><p><img src="/PublishingImages/Twitter-bird-blue-on-white_50x50.jpg" alt="" style="margin&#58;5px 10px;" />Follow the meeting on Twitter&#58; <a href="https&#58;//" target="_blank">#cicon15</a></p></div>
CAR T-Cell Therapy Trial Yields Early Promise for Lymphoma and Leukemia Patients19561879/16/2015 12:52:10 PM Releases/AllItems.aspx762False2015-09-16T13:00:00ZChemotherapy pretreatment may help improve outcomes with CAR T-cell therapy<div class="ExternalClass3C6D339F6BBE4B2FA94CA013ED59D200"><p>​NEW YORK — In a <a href="https&#58;//;rank=1" target="_blank">phase I/IIa trial</a>, third-generation CD19 CAR T-cell therapy combined with chemotherapy pretreatment resulted in complete response in some lymphoma and leukemia patients, according to data presented at the <a href="/Meetings/Pages/MeetingDetail.aspx?EventItemID=54" target="_blank">CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference</a>, held Sept. 16–19.</p><p><img alt="Angelica Loskog, PhD" src="/PublishingImages/Loskog_Angelica_150x200.jpg" style="margin&#58;10px;vertical-align&#58;auto;float&#58;right;" />&quot;Third-generation CAR T cells are being tested in clinical trials for leukemia patients in the United States with success, and so the main purpose of our clinical trial was to evaluate whether we could reproduce the successful results in leukemia patients in Sweden, and to also test if patients with lymphoma will respond to this treatment,&quot; said Angelica Loskog, PhD, professor of immunotherapy at Uppsala University in Sweden. The study is a collaborative effort between Uppsala University and Baylor College of Medicine in the United States and the first study presenting data using CD19 CAR T cells outside of the United States, according to Loskog.</p><p>Loskog explained that third-generation CAR T cells that target a protein called CD19 present on B cells are being tested in the United States with promising outcomes for patients with leukemia. Treating lymphomas with this type of therapy, however, has been challenging due to the higher concentration of immunosuppressive cells that can inhibit CAR T cells from doing their job. Further, barriers such as defective blood vessels and fibrotic tissue may make it difficult for CAR T cells to penetrate the tumor. Therefore, in a clinical trial, Loskog and colleagues tested whether a combination of shrinking tumors with chemotherapy and preconditioning to reduce the number of immunosuppressive cells might improve treatment outcomes.</p><p>&quot;Of the 11 patients recruited to this trial, six had complete responses,&quot; said Loskog. &quot;The complete responses in lymphoma patients despite the fact that they received only low doses of preconditioning compared with other published data surprised us. The strategy of both providing tumor-reductive chemotherapy for weeks prior to CAR T-cell infusion combined with preconditioning just before CAR T-cell infusion seems to offer promise.&quot;</p><p>Among the 11 patients Loskog; Hannah Karlsson, PhD, a researcher at Uppsala University; and colleagues enrolled in the clinical trial were four who had leukemia (acute lymphoblastic leukemia or chronic lymphocytic leukemia) and seven who had lymphoma (diffuse large B cell lymphoma or Burkitt lymphoma). All lymphoma patients received chemotherapy treatment three to 30 days before CAR T-cell therapy to lower their tumor burdens, and six patients (three with leukemia and three with lymphoma) received a preconditioning chemotherapy combination (cyclophosphamide plus fludarabine) one to two days before CAR T-cell therapy to lower immunosuppressive cell count. All patients received one infusion of CAR T cells as outpatients. Patients received one of the three doses tested.</p><p>Six patients, three with leukemia and three with lymphoma, had complete remission. Two of them relapsed later. Of the patients who had complete response, five had received preconditioning therapy. Cytokine release syndrome, a common side effect of CAR T-cell therapy, could be handled at the hospital and most patients had rapid relief of symptoms, according to Loskog.</p><p>&quot;Of the first five patients who did not receive preconditioning treatment the day before CAR T-cell infusion, only one had an initial complete response and the rest had rapid disease progression. In contrast, five of six patients who received preconditioning treatment had initial complete responses,&quot; Loskog said.</p><p>&quot;Our ongoing analyses will determine the number of immunosuppressive cells at different time points from enrollment, prior to T-cell infusion and multiple time points after T-cell infusion,&quot; Loskog said. &quot;To find means to manage the immunosuppressive cells over time without disturbing the CAR T-cell function will likely be of great importance for long-term complete responses for leukemia and lymphoma, but also for solid malignancies.&quot;</p><p>This study was funded by AFA Insurances AB and the Swedish Cancer Society. Loskog is the chief executive officer and board member of Lokon Pharma AB. She is the chairman of the board of Vivolux AB and RePos Pharma AB, and a scientific adviser of NEXTTOBE AB. She holds royalty agreements with Lokon Pharma AB and Alligator Bioscience AB. Karlsson declares no conflicts of interest.</p><p><img src="/PublishingImages/Twitter-bird-blue-on-white_50x50.jpg" alt="" style="margin&#58;5px 10px;" />Follow the meeting on Twitter&#58; <a href="https&#58;//" target="_blank">#cicon15</a></p></div>