Identification of HER-2/neu immunogenic epitopes presented by renal cell carcinoma and other human epithelial tumors.
HER-2/neu is a tumor-associated antigen overexpressed in a large variety of human tumors. Eight HER-2/neu peptides displaying HLA-A*0201 anchoring motifs were selected and tested for their binding affinity to HLA-A*0201 and their capacity to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*0201 transgenic mice and in HLA-A*0201(+) healthy donors. Two high-affinity (p5 and p48) and one intermediate-affinity (p1023) peptides triggered CTL responses in both transgenic mice and humans, comparable to those observed for the well-known HER2/neu dominant peptide p369. CTL induced in transgenic mice lysed HLA-A*0201(+) RMA cells infected with recombinant HER-2/neu but not cells infected with wild-type vaccinia virus. Human CTL lysed HLA-A*0201(+) HER-2/neu(+) tumor cells of different origins (breast, colon, lung and renal cancer) irrespective of the expression levels of HER-2/neu. Importantly, primed CTL specific for these epitopes were detected in freshly isolated tumor-infiltrating lymphocytes from three renal cell carcinoma patients. Therefore, the HER-2/neu peptides p5, p48 and p1023 may be good candidates for immunotherapy of a broad spectrum of tumors, including renal cell carcinoma.
Scardino
A
A
INSERM 487, Institut Gustave Roussy, Villejuif, France.
Alves
P
P
Gross
D A
DA
Tourdot
S
S
Graff-Dubois
S
S
Angevin
E
E
Firat
H
H
Chouaib
S
S
Lemonnier
F
F
Nadler
L M
LM
Cardoso
A A
AA
Kosmatopoulos
K
K
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy; D000939:Epitopes; D015234:HLA-A Antigens / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000939:Epitopes; D015234:HLA-A Antigens; D018719:Erb-b2 Receptor Tyrosine Kinases