Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides.
BACKGROUND
Tumor-associated lymphocytes (TAL) isolated from ovarian cancer patients contain cytotoxic T lymphocytes (CTL) capable of recognizing specific HLA/peptide complexes on tumor cells leading to tumor cell lysis. Currently, HER2/neu, overexpressed in only 30% of breast and ovarian cancers, is the only known source of CTL-recognized peptides in epithelial cancers. Therefore, we have investigated peptides derived from folate binding protein (FBP), which is over-expressed in more than 90% of ovarian cancers and in the majority of other epithelial tumors.


METHODS
TAL were isolated from the malignant ascites of four consecutive HLA-A2+ ovarian cancer patients and incubated in IL-2. Initial chromium-release assays were performed within 1 week. T2 cells, incubated with peptide, were used to reconstitute T cell epitopes. The FBP sequence was interrogated for HLA-A2 binding peptides, and five were synthesized (E37-41).


RESULTS
Freshly cultured, unstimulated ovarian TAL recognize peptides derived from FBP. These peptides are presented in the context of HLA-A2, and are specifically recognized in a HLA class I-restricted fashion. TAL recognition of these reconstituted T cell epitopes is concentration dependent. Furthermore, the FBP peptides are shown by cold target inhibition studies to be naturally processed and presented antigens.


CONCLUSIONS
FBP peptides are recognized by freshly isolated TAL from ovarian cancer patients, suggesting in vivo expression and sensitization. Because FBP is over-expressed 20-fold in most adenocarcinomas, these peptides may be used in a widely applicable peptide-based vaccine for epithelial tumors.
Peoples
G E
GE
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Anderson
B W
BW
Fisk
B
B
Kudelka
A P
AP
Wharton
J T
JT
Ioannides
C G
CG
D019496:Cancer Vaccines; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D015789:HLA-A2 Antigen; D010455:Peptides; D011956:Receptors, Cell Surface