Safety and efficacy of dendritic cell immunotherapy with ad-GMCAIX in an immunocompetent preclinical tumor model of renal cell carcinoma.

2017 
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,...
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