Oligopeptide induction of a cytotoxic T lymphocyte response to HER-2/neu proto-oncogene in vitro.
The HER-2/neu proto-oncogene (HER-2) encodes a transmembrane protein whose expression is enhanced in a number of breast and ovarian tumors and correlates with tumor aggressiveness. Because of its expression on normal epithelial cells, HER-2 can be defined as a tumor associated antigen and is of interest as a target of a therapeutic anti-tumor T cell response. To investigate whether oligopeptides analogs of HER-2 isolated from a likely target area of T cells can induce an anti-tumor CTL response, peripheral blood mononuclear cells were stimulated in vitro with HER-2 synthetic peptides. CTL cultures generated recognized peptides used as immunogen. A CD3+CD8+CD4- line isolated from these cultures lysed HLA-A2+, HER-2+ ovarian tumors but not natural killer target K562 cells, and showed significantly higher lysis of HER-2high than of HER-2low ovarian tumors. This lysis was inhibited by HER-2 peptide-pulsed HLA-A2+ targets, suggesting that similar epitopes are presented on tumor cells associated with HLA-A2. The observation that peptide analogs of a proto-oncogene can induce CTL in vitro which express tumor lysis dependent on the levels of expression of HER-2 is novel for human tumor systems. Targeting by T cells of HER-2 may prove useful for understanding the mechanisms of recognition, tolerance, and therapeutic use of human tumor reactive T cells.
Fisk
B
B
Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Chesak
B
B
Pollack
M S
MS
Wharton
J T
JT
Ioannides
C G
CG
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology; D010455:Peptides / Q000276:immunology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D066246:ErbB Receptors; D010455:Peptides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human