Dendritic Cell–Based Immunotherapy in Prevention and Treatment of Renal Cell Carcinoma

• DOI: 10.1097/cji.0b013e31827bec97
• Publication Date: 2013-01-31T13:19:36Z
• Authors: Frédéric D. Birkh...; Richard C. Koya; Caleb Neufeld; Edward N. Rampersaud; Xuyang Lu; Ewa D. Micewicz; Thinle Chodon; Mohammad Atefi; Nils Kroeger; Gadisetti V.R. Ch...; Gang Li; Jonathan W. Said; William H. McBride; Fairooz F. Kabbin...; Antoni Ribas; Allan J. Pantuck; Arie S. Belldegrun; Joseph Riss
• Keywords: Immunoediting

The dendritic cell vaccine DC-Ad-GM·CAIX is an active, specific immunotherapy with the potential of providing a safe and effective therapy against renal carcinoma (RCC). Using immunocompetent Balb/c mouse models we tested efficacy mechanism to prevent treat growth syngeneic RCC (RENCA) engineered overexpress human TAA carbonic anhydrase IX (NPR-IX). In prevention model, NPR-IX tumor development was specifically significantly delayed by 13 days in DC-Ad-GM·CAIX-treated mice (P<0.001), volumes were 79% smaller (day 24, P<0.007), body weight maintained at study termination compared controls. Six these remained tumor-free for >1 year. treatment tumors 8 (P<0.002), achieving 60% inhibition termination. No vaccine-related organ toxicity observed either model. critical mechanistic parameter separating responsive from nonresponsive hCAIX protein expression, demonstrated aggressive that did not express sham-treated (DC-Ad-Null). murine serum anti-hCAIX antibodies detected. Moreover, altered mechanisms immunoediting as means immune evasion suggested differential gene expression (Ccl1, Hmgb1, Fgl2, Cd209a, Klra2) miRNAs (miR-1186, miR-98, miR-5097, miR-1942, miR-708) evaded immunotherapy. This first provides proof concept specificity, efficacy, safety, activity immunotherapy, forming basis first-in-human phase I trial patients.