Abstract 1563: In vivo safety and efficacy of a novel dendritic cell based Ad-GMCAIX vaccine with activity against renal cell carcinoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.1563-1563
• Main Authors: Birkhäuser, Frédéric D., Koya, Richard C., Neufeld, Caleb, Lu, Xuyang, Micewicz, Ewa D., Chodon, Thinle, Atefi, Mohammad, Kroeger, Nils, Rampersaud, Edward N., Chandramouli, Gadisetti VR, Li, Gang, Said, Jonathan W., Ribas, Antoni, McBride, William H., Kabbinavar, Fairooz F., Pantuck, Allan J., Belldegrun, Arie S., Riss, Joseph
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-1563

Carbonic anhydrase IX (CAIX) expression is constitutively up-regulated in clear cell renal cell carcinoma (ccRCC) due to loss of the VHL gene. Its up-regulation in ccRCC and low expression levels in normal tissues led us to develop an immunotherapeutic approach targeting the CAIX tumor antigen. We previously reported the successful generation and ex vivo priming of CAIX-specific, MHC restricted cytotoxic T lymphocytes (CTLs) by adenoviral (Ad) transduction of the GM-CAIX fusion protein in dendritic cells (DCs). Our current study tests, for the first time, the in vivo anti-tumor activity of DC-Ad-GMCAIX in preventing and intervening in the growth of RCC in immunocompetent mouse models. Tumor growth was studied in BALB/c mice transplanted s.c. with either the syngeneic CAIX-expressing RCC cell line RENCA-CAIX (PRCAIX) or the non-CAIX-expressing parental RENCA line. In the preventative model, cohorts of mice were s.c. immunized twice 6 days apart with either DC-Ad-GMCAIX, DC-Ad-null, or no DC transplantation, followed by s.c. challenge with PRCAIX or RENCA lines 12 days later. In the interventional model, tumors were first established and then immunotherapy was employed. At the end of each study, tumors were harvested, and partial necropsy, immunohistochemistry, and complete blood count were performed. DC-Ad-GMCAIX expressed in vivo the hCAIX protein that primed CTLs to specifically target hCAIX expressed by the PRCAIX line. In the preventative model, PRCAIX tumor growth was specifically and significantly inhibited by DC-Ad-GMCAIX for 15 days (all p