SU2C-Farrah Fawcett Foundation Human Papillomavirus (HPV) Translational Research Team Grant: Therapeutic CD8 vaccines against conserved E7 HPV epitopes identified by MS
Ellis L. Reinherz, MD
Chief, Laboratory of Immunobiology; co-director, Cancer Vaccine Center,
Dana-Farber Cancer Institute; professor of medicine, Harvard Medical School
Robert I. Haddad, MD
Chief, Head and Neck Oncology Program; member, Department of Adult Oncology, Dana-Farber Cancer Institute; associate professor of medicine,
Harvard Medical School
Worldwide, persistent infection with certain types of human papillomavirus (HPV) is responsible for more than 5 percent of all new human cancer cases. These viruses play a significant role in cancers of the cervix, vulva, vagina, anus, penis, head, and neck. Although vaccines can help prevent infection with the HPV types that cause the most cancer cases, these vaccines do not benefit people once they have already become infected.
Once a cancer-causing type of HPV has established itself, immune cells called cytolytic T lymphocytes (CTLs) are required to eradicate the virus-infected precancerous or cancerous cells. CTLs distinguish between the body’s own good cells and those that are abnormal by recognizing “tags” on the surface of the abnormal cells. More specifically, CTLs have molecules called T-cell receptors (TCRs) that detect “tags” called epitopes on the surface of cells. Using their TCRs, CTLs can distinguish between normal and abnormal cells with great specificity. Since CTLs are able to distinguish abnormal epitopes in a sea of 100,000 normal epitopes, these cells are ideal for development of therapeutic vaccines that stimulate the right CTLs to attack virus-infected, pre-cancerous or cancerous cells.
The multidisciplinary research team led by Reinherz and Haddad includes molecular and cellular immunologists, an ion physicist, a computer scientist, a vaccinologist, a molecular oncologist, and translational scientists. The team will focus on patients with HPV-driven cancers (including cervical, anal, and head and neck cancer) who relapse following initial therapy. These patients have few therapeutic options, and the team’s aim is to develop novel immunotherapy approaches that will address this huge unmet need.
The researchers have developed a highly sensitive ion physics method to find epitopes on cancer cells that are entirely specific for the cancer and hence not found on the normal cells in the body. These epitopes can signal to receptors on the CTLs, to attack and kill the cancer once CTL are programmed by vaccination to do so in the patient’s body. One CTL target that the team has already identified has been incorporated into a new therapeutic vaccine that will be tested on patients in a clinical trial as part of this research grant. The team will also use their epitope-identification technology to find other epitopes for the development of additional immunotherapeutic agents. Finally, they will identify the T-cell receptors on CTLs that provide the best immune response in order to re-engineer the patients’ own immune cells in the laboratory for use as a cancer treatment.
The innovative approaches to be pursued here will lead to novel immunotherapies that have the potential to dramatically improve outcomes for patients with HPV-driven cancers who relapse following initial therapy.
Amount Of Funding:
$1.2 million over a three-year period
Cornelia Trimble, MD, Johns Hopkins University
Updated: May 2016