American Association for Cancer Research

July 15 Clinical Cancer Research Highlights

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Selected Articles from the July 15, 2005 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the July 15 issue of Clinical Cancer Research.


CD40-Activated MCL Cells Key to Allogenic T-Cell Response

Hoogendoorn et al.
Page 5310

To potentiate the graft-versus-lymphoma effect in patients treated with an allogeneic stem cell transplantation for advanced mantle cell lymphoma (MCL), the adoptive transfer of MCL-specific cyotoxic T-cells (CTLs) can be an attractive approach. To reverse T-cell anergy to primary MCL cells, Hoogendoorn et al. modified MCL cells into dedicated antigen-presenting cells by CD40 activation. These MCL-APC cells as stimulator cells were capable of inducing MCL-reactive CD8+ CTL clones from HLA class I–matched donors, demonstrating the feasibility of generating primary allogeneic T-cell responses against MCL-APC. The application of MCL-reactive CTLs could prevent or treat disease recurrence after allogeneic SCT.


COX Levels in Breast Cancer Relapses Suggest Role for Inhibitors

Kim et al.
Page 5199

Kim et al. examined paraffin-embedded specimens from post-mastectomy chest wall relapses, all treated with primary radiation therapy, which were retrieved from 38 patients, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0-3+. A score of 2-3+ was considered positive. COX was considered positive in 13 of 38 cases. COX was inversely correlated with ER (P = .045) and PR (P = .028), and positively correlated with HER-2/neu (P = .003). COX was also associated with a shorter time to chest wall relapse. The distant metastasis-free rate for COX-negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2–positive patients (P = 0.029). COX-positive patients had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX-negative patients (P < .003). If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for PMCWR.


Presurgical Docetaxel for High-Risk Prostate Cancer

Febbo et al.
Page 5233

Some prostate cancer patients are at risk of having microscopic metastases at the time of diagnosis and are not cured with single modality treatment (surgery or radiation therapy). Febbo et al. gave men with high-risk, localized prostate cancer 6 months of weekly docetaxel chemotherapy before surgery to assess clinical and genomic responses. Clinically, 58% had at least a 50% decline in their serum PSA, but no patient had a pathologic complete response. Microarray analysis comparing docetaxel-treated tumors with untreated tumors suggests that cancer cells may decrease intratumoral androgen levels to resist chemotherapy. This study demonstrates that neoadjuvant docetaxel is feasible, induces declines in PSA, and implicates altered androgen metabolism as a chemotherapeutic survival mechanism in prostate cancer.


IOCT Affords Precision Noninvasive Monitoring after Radiation

Muanza et al.
Page 5121

Optical coherence tomography (OCT) imaging was evaluated in a murine mucositis model to determine if radiation-induced mucosal damage could be noninvasively monitored and correlated with histopathologic findings. Muanza et al. collected OCT images over a 7-day period following single- dose radiation treatment; histologic samples were taken on day 7. OCT detected mucosal changes after irradiation, before visual manifestation, by both visual inspection of the images and by quantitative image analysis. OCT may be useful for real-time monitoring of subclinical tissue injury during experimental radiation and combined modality trials in which novel radiation modifiers could be evaluated noninvasively without reaching high-grade toxicity.


Metal-Labeled Antibody Fragment Enhances Pharmacodynamics and Kidney Tumor Imaging

Grünberg et al.
Page 5112

The L1 cell adhesion protein is involved in tumor cell proliferation and is overexpressed in neuroblastomas, renal cell, ovarian, and endometrial carcinomas where it is emerging as a target for diagnosis and therapy. Grünberg et al. observed that recombinant F(ab’)2 fragments of the internalizing anti-L1 antibody chCE7 labeled with copper-67/64 and lutetium-177 combine high yield protein production with improved clearance and biodistribution properties. PET imaging with copper-64-chCE7F(ab’)2 allows clear visualization of subcutaneous xenografts and peritoneal metastases. For radioimmunotherapy, both copper-67- and lutetium-177-chCE7 conjugates are suitable. The matched pair copper-64/67-chCE7F(ab’)2 with its superior tumor/kidney ratios is a promising radiopharmaceutical for PET imaging and radioimmunotherapy of L1-expressing tumors.