Evaluation of renal cell carcinoma vaccines targeting carbonic anhydrase IX using heat shock protein 110.
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-gamma 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-gamma 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-gamma 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.
Kim
Hyung L
HL
Department of Urologic Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. hyung.kim@roswellpark.org
Sun
Xiaolei
X
Subjeck
John R
JR
Wang
Xiang-Yang
XY
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000276:immunology* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D050957:HSP110 Heat-Shock Proteins / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D050957:HSP110 Heat-Shock Proteins; D011994:Recombinant Proteins; D002256:Carbonic Anhydrases