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View the Table of Contents for the August 15 issue of Clinical Cancer Research.
Tassi et al. Page 4949
Renal cell carcinoma (RCC) is immunogenic; nonetheless, rare tumor antigens have been identified. To verify whether peptidome from RCC is immunogenic, Tassi et al. used autologous dendritic cells loaded with RCC peptidome from allogenic tumors to activate CD4+ T cells in vitro. CD4+ T cells recognized HLA-DR-matched allogenic RCCs, tumors of different histology, and the autologous tumor, but not normal cells, supporting the peptidome approach for RCC immunotherapy. Interestingly, CD4+ T cells comprise both Th1 and Th2/Th0 cells all endowed with cytolytic activity, suggesting that activation of both effector subsets may be implicated in antitumor immunity.
Salinger et al. Page 4888
Patients frequently receive chemotherapy dosages based on their body weight or body surface area; however, there are wide patient-to-patient variations in the pharmacokinetics of these drugs, leading to clinically significant differences in the efficacy or toxicity of chemotherapy (i.e., pharmacodynamics). Salinger et al. address the dose individualization of cyclophosphamide, with the intent of decreasing the toxicity of this drug while preserving its effectiveness in patients undergoing hematopoietic cell transplant for hematologic malignancy. Using an individual patient’s pharmacokinetic data along with the Bayesian model, the authors estimate the area under the curve of two key cyclophosphamide metabolites to more accurately conduct real-time cyclophosphamide dose-adjustment.
Fox et al. Page 4882
ABT-751 is an orally bioavailable sulfonamide that binds the colchicine site of β-tubulin and inhibits microtubule polymerization. Fox et al. conducted a dose escalation study of ABT-751 in children (n = 24) with refractory solid tumors. The recommended dose of ABT-751 was 200 mg/m2 daily for 7 days every 21 days. Dose-limiting toxicities were neuropathy, fatigue, and hypertension. Five of 8 children with neuroblastoma evaluated by metaiodobenzylguanidine scintigraphy had prolonged stable disease and remained on the study for 5, 7, 27, 41, and 50 cycles of therapy. A phase 2 trial of ABT-751 in children with neuroblastoma is in development.
Liu et al. Page 4958
Pretargeting is an improved method for cancer radiotherapy over direct targeting with radiolabeled antibodies. Liu et al. report on the first use of phosphorodiamidate morpholino oligomers (MORF) pretargeting for cancer therapy. Their novel pretargeting approach uses two complementary DNA analogues, MORF and cMORF, chosen for their strong hybridization affinities and considerable promise in nuclear imaging of tumored mice. Mice received MORF-antitumor antibody two days before receiving the complementary cMORF radiolabeled with rhenium-188. Tumor growth in the pretargeting study group ceased one day after radioactivity injection while tumors continued to grow at the same rate among the three control groups.