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MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.

Publication ,  Journal Article
Morse, MA; Secord, AA; Blackwell, K; Hobeika, AC; Sinnathamby, G; Osada, T; Hafner, J; Philip, M; Clay, TM; Lyerly, HK; Philip, R
Published in: Clin Cancer Res
May 15, 2011

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.

Duke Scholars

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 15, 2011

Volume

17

Issue

10

Start / End Page

3408 / 3419

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Proteomics
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Lymphocyte Activation
  • Immunoprecipitation
  • Humans
  • Histocompatibility Antigens Class I
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Morse, M. A., Secord, A. A., Blackwell, K., Hobeika, A. C., Sinnathamby, G., Osada, T., … Philip, R. (2011). MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer. Clin Cancer Res, 17(10), 3408–3419. https://doi.org/10.1158/1078-0432.CCR-10-2614
Morse, Michael A., Angeles A. Secord, Kimberly Blackwell, Amy C. Hobeika, Gomathinayagam Sinnathamby, Takuya Osada, Julie Hafner, et al. “MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.Clin Cancer Res 17, no. 10 (May 15, 2011): 3408–19. https://doi.org/10.1158/1078-0432.CCR-10-2614.
Morse MA, Secord AA, Blackwell K, Hobeika AC, Sinnathamby G, Osada T, et al. MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer. Clin Cancer Res. 2011 May 15;17(10):3408–19.
Morse, Michael A., et al. “MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.Clin Cancer Res, vol. 17, no. 10, May 2011, pp. 3408–19. Pubmed, doi:10.1158/1078-0432.CCR-10-2614.
Morse MA, Secord AA, Blackwell K, Hobeika AC, Sinnathamby G, Osada T, Hafner J, Philip M, Clay TM, Lyerly HK, Philip R. MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer. Clin Cancer Res. 2011 May 15;17(10):3408–3419.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 15, 2011

Volume

17

Issue

10

Start / End Page

3408 / 3419

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Proteomics
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Middle Aged
  • Lymphocyte Activation
  • Immunoprecipitation
  • Humans
  • Histocompatibility Antigens Class I
  • Female