1. Safety and efficacy of dendritic cell immunotherapy with ad-GMCAIX in an immunocompetent preclinical tumor model of renal cell carcinoma
- Author
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Antoni Ribas, Ewa D. Micewicz, Frédéric D. Birkhäuser, Gadisetti V.R. Chandramouli, Caleb Neufeld, Nils Kroeger, Richard C. Koya, Thinle Chodon, William H. McBride, Gang Li, Joseph Riss, Fairooz F. Kabbinavar, Arie S. Belldegrun, Mohammad Atefi, Jonathan W. Said, Allan J. Pantuck, Edward N. Rampersaud, and Xuyang Lu more...
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Cancer Research ,business.industry ,medicine.medical_treatment ,Dendritic cell ,Immunotherapy ,medicine.disease ,Fusion protein ,Transplantation ,Oncology ,In vivo ,Renal cell carcinoma ,Cancer research ,Cytotoxic T cell ,Medicine ,business ,Ex vivo - Abstract
e13045 Background: We have previously reported the successful ex vivo generation of hCAIX-specific cytotoxic T lymphocytes (CTLs) by adenoviral (Ad) transduction of the GMCAIX fusion protein in dendritic cells (DC). We then produced GMP-grade material (NIH-RAID program, NSC 740833). Now we test, for the first time, the in vivo anti-tumor activity of DC-Ad-GMCAIX against renal cell carcinoma (RCC) in a unique immunocompetent mouse tumor model. Methods: Tumor growth inhibition and specificity were studied in BALB/c mice s.c. transplanted with either syngeneic RENCA cells transduced with hCAIX (URCAIX) or with non-hCAIX-expressing RENCA cells (RENCA). In a tumor prevention model, cohorts of mice were first immunized s.c. twice with DC-Ad-GMCAIX, DC-Ad-null, or no DCs, followed by tumor challenge with s.c. transplantation of URCAIX or RENCA cells. In an intervention model, tumors were first established and then immunotherapy was employed. Tumor volume and body weight were regularly assessed. Partial necropsy, immunohistochemistry of harvested tumors, and complete blood count were performed at termination of each study. Results: In the prevention model, URCAIX tumor growth was specifically and significantly inhibited for 15 days (p3) and half of the mice remained tumor-free. In the intervention model, DC-Ad-GMCAIX-treated mice showed specific and significant growth inhibition of URCAIX tumors for 8 days (p3). The threshold of 15% weight loss was delayed in the therapeutic groups of both models (p more...
- Published
- 2012
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