Annals of Surgical Oncology, Vol 5, Issue 8 743-750, Copyright © 1998 by Society of Surgical Oncology

ARTICLES

Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides

G. E. Peoples, B. W. Anderson, B. Fisk, A. P. Kudelka, J. T. Wharton and C. G. Ioannides
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

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.

This article has been cited by other articles:

				K. L. Knutson, C. J. Krco, C. L. Erskine, K. Goodman, L. E. Kelemen, P. J. Wettstein, P. S. Low, L. C. Hartmann, and K. R. Kalli T-Cell Immunity to the Folate Receptor Alpha Is Prevalent in Women With Breast or Ovarian Cancer J. Clin. Oncol., September 10, 2006; 24(26): 4254 - 4261. [Abstract] [Full Text] [PDF]

				K. L. Bondurant, M. D. Crew, A. D. Santin, T. J. O'Brien, and M. J. Cannon Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme Clin. Cancer Res., May 1, 2005; 11(9): 3446 - 3454. [Abstract] [Full Text] [PDF]

				J. I. Risinger, G. L. Maxwell, G. V. R. Chandramouli, A. Jazaeri, O. Aprelikova, T. Patterson, A. Berchuck, and J. C. Barrett Microarray Analysis Reveals Distinct Gene Expression Profiles among Different Histologic Types of Endometrial Cancer Cancer Res., January 1, 2003; 63(1): 6 - 11. [Abstract] [Full Text] [PDF]

				L. H. Butterfield, W. S. Meng, A. Koh, C. M. Vollmer, A. Ribas, V. B. Dissette, K. Faull, J. A. Glaspy, W. H. McBride, and J. S. Economou T Cell Responses to HLA-A*0201-Restricted Peptides Derived from Human {{alpha}} Fetoprotein J. Immunol., April 15, 2001; 166(8): 5300 - 5308. [Abstract] [Full Text] [PDF]

				J. Gong, N. Nikrui, D. Chen, S. Koido, Z. Wu, Y. Tanaka, S. Cannistra, D. Avigan, and D. Kufe Fusions of Human Ovarian Carcinoma Cells with Autologous or Allogeneic Dendritic Cells Induce Antitumor Immunity J. Immunol., August 1, 2000; 165(3): 1705 - 1711. [Abstract] [Full Text] [PDF]

				G. E. Peoples, B. W. Anderson, T. V. Lee, J. L. Murray, A. P. Kudelka, J. T. Wharton, and C. G. Ioannides Vaccine Implications of Folate Binding Protein, a Novel Cytotoxic T Lymphocyte-recognized Antigen System in Epithelial Cancers Clin. Cancer Res., December 1, 1999; 5(12): 4214 - 4223. [Abstract] [Full Text] [PDF]