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Ann Surg Oncol. 1998 Dec;5(8):743-50.

Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides.

Author information

1
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Abstract

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.

PMID:
9869522
[Indexed for MEDLINE]

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