Induction of antigen specific cellular immunity by vaccination with peptides from MN/CA IX in renal cell carcinoma.
We investigated the induction of the specific immunity for renal cell carcinomas (RCC) using MN/CA IX, a tumor-associated antigen frequently expressed in RCC. We have generated 9-mer peptide derived from MN/CA IX and examined the antigenicity as a vaccine to induce specific immunity for RCC. To use mouse syngeneic system, we transfected human MN/CA9 cDNA into RenCa and BALB-3T3 cells originally from BALB/c mouse, and established MN/CA IX expressing mouse cell lines, i.e., MN-RenCa and MN-3T3. The immunization of BALB/c mouse with MN-RenCa cells resulted in the induction of cytotoxic T lymphocytes (CTL) against MN/CA IX expressing cells and the CTL clone was established from bulked CTL. This CTL clone specifically lyzed MN-3T3 cells, but not parental cells. To identify the targeted epitope binding to H-2Kd antigen, three 9-mer peptides (A, B, C-peptide) of human MN/CA IX compatible with the H-2Kd as well as HLA-A24 binding motif was synthesized. The cloned CTL targeted the B-peptide pulsed BALB-3T3 cells as well as MN-3T3 cells. Furthermore, spleen cells from BALB/c mouse immunized with B-peptide reacted against MN-RenCa cells. These results suggest that the peptides derived from MN/CA IX containing HLA-A24 binding motif may be useful as a potent tumor vaccine for the treatment of human RCC, and in mouse models.
Shimizu
Kazuhiro
K
Department of Urology, Nara Medical University, Nara 634-0813, Japan.
Uemura
Hirotsugu
H
Yoshikawa
Motoyoshi
M
Yoshida
Katsunori
K
Hirao
Yoshihiko
Y
Iwashima
Kumiko
K
Saga
Shinsuke
S
Yoshikawa
Kazuhiro
K
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry; D019496:Cancer Vaccines; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000517:prevention & control* / Q000628:therapy*; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007680:Kidney Neoplasms / Q000517:prevention & control* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018076:DNA, Complementary; D000939:Epitopes; D009363:Neoplasm Proteins; D010455:Peptides; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases