Evaluation of renal cell carcinoma vaccines targeting carbonic anhydrase IX using heat shock protein 110 |
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Authors: | Hyung L Kim Xiaolei Sun John R Subjeck Xiang-Yang Wang |
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Institution: | (1) Department of Urologic Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA;(2) Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA |
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Abstract: | Carbonic anhydrase IX (CA9) is a renal cell carcinoma (RCC)-specific tumor protein that is targeted using heat shock protein
110 (hsp110). The chaperoning ability of hsp110 can be utilized to form a complex with CA9 (hsp110 + CA9) in vitro, which
can be administered as a highly concentrated tumor vaccine. In a tumor prevention model, hsp110 + CA9 prevented the growth
of RENCA tumors in BALB/c mice, and produced IFN-γ response measured using ELISPOT and an antibody response measured using
ELISA. To test a second vaccine strategy, hsp110 complexed to a previously described CA9 peptide prevented tumor growth and
produced a very weak IFN-γ response, but no antibody response. A plasmid vector containing grp170, a member of the hsp110
family, linked to CA9 did not produce an antitumor response and produced no IFN-γ response or antibodies. In a model of metastatic
RCC, RENCA cells were injected intradermally prior to vaccination. Hsp110 + CA9 decreased tumor growth compared to control
vaccinations. These studies suggest that recombinant hsp110 complexed to CA9 should be evaluated for treatment of RCC. |
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Keywords: | Renal cell carcinoma Carbonic anhydrase IX Heat shock protein Tumor vaccine RENCA Heat shock protein 110 |
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