MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.
Journal Article
PURPOSE: The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans. EXPERIMENTAL DESIGN: Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials. RESULTS: T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells. CONCLUSION: Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients.
Full Text
Duke Authors
- Blackwell, Kimberly Lynn
- Hobeika, Amy Claudine
- Lyerly, Herbert Kim
- Morse, Michael Aaron
- Osada, Takuya
- Secord, Angeles Alvarez
Cited Authors
- Morse, MA; Secord, AA; Blackwell, K; Hobeika, AC; Sinnathamby, G; Osada, T; Hafner, J; Philip, M; Clay, TM; Lyerly, HK; Philip, R
Published Date
- May 15, 2011
Published In
Volume / Issue
- 17 / 10
Start / End Page
- 3408 - 3419
PubMed ID
- 21300761
Pubmed Central ID
- 21300761
Electronic International Standard Serial Number (EISSN)
- 1557-3265
Digital Object Identifier (DOI)
- 10.1158/1078-0432.CCR-10-2614
Language
- eng
Conference Location
- United States