Generation of RAGE-1 and MAGE-9 peptide-specific cytotoxic T-lymphocyte lines for transfer in patients with renal cell carcinoma.
Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysate-pulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE-1 and MAGE-9 peptide-specific CTL lines. RAGE-1 and MAGE-9 are expressed in 56% and 38% of RCCs. Seven MAGE-9- and 13 RAGE-1-derived peptides were found to be immunogenic in the context of the HLA-A*0201 MHC. CTLs were generated by coculture with peptide-pulsed, activated B cells, which were easily generated in great quantities and displayed functional activity for a prolonged period of time. MAGE-9 and RAGE-1 peptide-specific CTL lines were strictly peptide-specific and displayed high cytotoxic activity not only against peptide-loaded T2 cells but also against HLA-A*0201-positive RCC lines, which naturally express MAGE-9, RAGE-1 or both. Thus, B cells are well suited as APCs for the generation of large numbers of tumor peptide-specific CTLs for adoptive transfer. MAGE-9 as well as RAGE-1 may well provide suitable targets for immunotherapy of RCC.
Oehlrich
Nicole
N
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany.
Devitt
Gerard
G
Linnebacher
Michael
M
Schwitalle
Yvette
Y
Grosskinski
Sonja
S
Stevanovic
Stefan
S
Zöller
Margot
M
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen; D006801:Humans; D008285:Major Histocompatibility Complex; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D010446:Peptide Fragments / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C505356:MAGE-9 antigen, human; D010446:Peptide Fragments; C498978:MOK protein, human; D020928:Mitogen-Activated Protein Kinases