BERKELEY, CA (UroToday.com) - Carbonic anhydrase IX (CA9) is a renal cell carcinoma (RCC) specific cell membrane protein that has been implicated in the lethality of RCC.

It is expressed in more than 80% of primary and metastatic RCC's, particularly the more common clear cell variant. Heat shock proteins (HSP's) are cellular chaperones that bind and protect partially denatured proteins, and these HSP's can be harnessed for vaccine development. Oncophage (vitespen) is one such vaccine technology that utilized HSP's as a platform to present tumor specific antigens as a vaccine strategy. In preclinical studies using a RENCA model, Kim and colleagues examine the efficacy of an HSP 110:CA9 vaccine formulation as a treatment strategy for RCC.

The authors used a RENCA model of RCC in mice that is genetically engineered to express CA9. The authors then tested 3 different CA9 vaccine formulations: full length recombinant CA9 combined with hsp110, a CA9 peptide in combination with hsp110, and a DNA vaccine formulation with CA9 fused to the HSP grp170. In their initial experiments, the authors vaccinated mice with the different vaccine strategies and then injected tumor cells and monitored animals for evidence of tumor growth (mimicking an adjuvant therapy model). Mice injected with full length CA9 with hsp110 demonstrated no evidence of tumor growth at 40 days. Injection with the CA9 peptide: hsp110 formulation inhibited but did not prevent tumor growth. The DNA vaccine with CA9 fused to grp170 had no antitumoral activity in this model. Mice injected with the full length CA9:hsp110 formulation developed anti-CA9 antibodies and a CA-9 specific IFN gamma response on Elispot. In another experiment, administration of the full length CA9:hsp110 vaccine to mice with existing RENCA tumors significantly inhibited the growth of tumors (p=0.0001) relative to controls, although no tumor regression was noted.

CA9 is a RCC specific molecular target that has been exploited in many strategies for RCC treatment. These include antibody strategies and now, vaccine strategies that target this molecule. These preclinical studies suggest that vaccines utilizing full length CA9 in combination with hsp110 may be an effective strategy for targeting CA9 in clinical studies. One concern that the model used in this study does not address is the possibility of toxicity from reaction with normal tissues that express CA9 (such as bile duct epithelium), which may hinder clinical development of this strategy.

Kim H.L, Sun X, Subjeck J.R, Wang X.Y

Cancer Immunology, Immunotherapy. 56(7):1097-1105, July 2007.
doi: 10.1007/s00262-006-0258-z

UroToday.com Renal Cancer Section

Written by Christopher G. Wood, MD, a Contributing Editor with UroToday.

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