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Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides

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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.

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Authors and Affiliations

  1. the Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

    Brett W. Anderson BS, Bryan Fisk MS, J. Taylor Wharton MD & Constantin G. Ioannides PhD

  2. the Department of Gynecologic Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

    Andrzej P. Kudelka MD

  3. the Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

    Constantin G. Ioannides PhD

  4. the Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland

    George E. Peoples MD

  5. Dept. of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 106, 77030, Houston, TX

    George E. Peoples MD

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Peoples, G.E., Anderson, B.W., Fisk, B. et al. Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides. Annals of Surgical Oncology 5, 743–750 (1998). https://doi.org/10.1007/BF02303486

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  • DOI: https://doi.org/10.1007/BF02303486

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