Shared T cell epitopes in epithelial tumors.
We have previously shown the importance of human leukocyte antigen (HLA)-A2 and the proto-oncogene HER2/neu in the T cell recognition of ovarian cancer. Since these proteins are ubiquitously expressed in epithelial-derived tumors, we have acid-eluted HLA-bound peptides from ovarian cancers, fractionated the peptides, and reconstituted T cell epitopes on the HLA-A2+ T2 cell line to determine if common tumor-associated antigens exist among HLA-A2+, HER2/neu+ epithelial cancers. We demonstrate that tumor-specific cytotoxic T lymphocytes (CTL) generated from tumor-infiltrating lymphocytes isolated from three ovarian, two breast, and two non-small-cell lung cancers recognize at least three of the same peptide fractions from multiple elutions. One of these peptide fractions coelutes with a HER2/neu-derived peptide which has been shown recently to be recognized by these same CTL. These findings demonstrate that a common peptide-based tumor vaccine is theoretically possible for many different epithelial-derived cancers.
Peoples
G E
GE
Laboratory of Biological Cancer Therapy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Smith
R C
RC
Linehan
D C
DC
Yoshino
I
I
Goedegebuure
P S
PS
Eberlein
T J
TJ
D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D004848:Epithelium / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D010455:Peptides; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human