Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides

Ann Surg Oncol. 1998 Dec;5(8):743-50. doi: 10.1007/BF02303486.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cancer Vaccines*
  • Carrier Proteins / chemistry
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Female
  • Folate Receptors, GPI-Anchored
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism
  • Humans
  • Ovarian Neoplasms / immunology*
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Tumor Cells, Cultured


  • Cancer Vaccines
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • HLA-A2 Antigen
  • Peptides
  • Receptors, Cell Surface