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Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme.
Clin Cancer Res. 2005 May 01; 11(9):3446-54.CC

Abstract

PURPOSE

The serine protease stratum corneum chymotryptic enzyme (SCCE) is overexpressed by ovarian tumor cells, but is not expressed by normal tissues, suggesting that SCCE may be an attractive target for immunotherapy. In this study, we tested the hypothesis that dendritic cells loaded with SCCE peptides will induce ovarian tumor antigen-specific CD8+ CTL responses and antigen-specific CD4+ helper T cell responses.

EXPERIMENTAL DESIGN

Computer algorithms were used to identify candidate HLA-A2.1-restricted CD8+ CTL epitopes and HLA-DR-binding CD4+ helper T cell epitopes within SCCE. CD8+ CTL stimulated with peptide-loaded dendritic cells were tested against targets expressing endogenous SCCE, including HLA-A2.1-matched ovarian tumor cells. Dendritic cells were also loaded with an extended SCCE peptide, SCCE 110-139, which encompassed a defined CD8+ CTL epitope and multiple candidate CD4+ T helper cell epitopes.

RESULTS

CD8+ CTL specific for SCCE 123-131 lysed autologous macrophages infected with an SCCE-expressing recombinant adenovirus, and also lysed HLA-A2.1-matched, SCCE-expressing ovarian tumor cells. Dendritic cells loaded with SCCE 5-13 peptide stimulated an HLA-A2.1-restricted CD8+ CTL response, but with a reduced level of lysis against ovarian tumor cells. Dendritic cells loaded with SCCE 110-139 induced antigen-specific CD4+ T cell and CD8+ T cell responses. Although SCCE 110-139-loaded dendritic cells processed and presented the 123-131 epitope, the dominant CD8+ CTL response was directed against alternative epitopes within SCCE 110-139.

CONCLUSIONS

The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer.

Authors+Show Affiliations

Department of Microbiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15867247

Citation

Bondurant, Kristina L., et al. "Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 9, 2005, pp. 3446-54.
Bondurant KL, Crew MD, Santin AD, et al. Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme. Clin Cancer Res. 2005;11(9):3446-54.
Bondurant, K. L., Crew, M. D., Santin, A. D., O'Brien, T. J., & Cannon, M. J. (2005). Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(9), 3446-54.
Bondurant KL, et al. Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme. Clin Cancer Res. 2005 May 1;11(9):3446-54. PubMed PMID: 15867247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme. AU - Bondurant,Kristina L, AU - Crew,Mark D, AU - Santin,Alessandro D, AU - O'Brien,Timothy J, AU - Cannon,Martin J, PY - 2005/5/4/pubmed PY - 2005/8/2/medline PY - 2005/5/4/entrez SP - 3446 EP - 54 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 11 IS - 9 N2 - PURPOSE: The serine protease stratum corneum chymotryptic enzyme (SCCE) is overexpressed by ovarian tumor cells, but is not expressed by normal tissues, suggesting that SCCE may be an attractive target for immunotherapy. In this study, we tested the hypothesis that dendritic cells loaded with SCCE peptides will induce ovarian tumor antigen-specific CD8+ CTL responses and antigen-specific CD4+ helper T cell responses. EXPERIMENTAL DESIGN: Computer algorithms were used to identify candidate HLA-A2.1-restricted CD8+ CTL epitopes and HLA-DR-binding CD4+ helper T cell epitopes within SCCE. CD8+ CTL stimulated with peptide-loaded dendritic cells were tested against targets expressing endogenous SCCE, including HLA-A2.1-matched ovarian tumor cells. Dendritic cells were also loaded with an extended SCCE peptide, SCCE 110-139, which encompassed a defined CD8+ CTL epitope and multiple candidate CD4+ T helper cell epitopes. RESULTS: CD8+ CTL specific for SCCE 123-131 lysed autologous macrophages infected with an SCCE-expressing recombinant adenovirus, and also lysed HLA-A2.1-matched, SCCE-expressing ovarian tumor cells. Dendritic cells loaded with SCCE 5-13 peptide stimulated an HLA-A2.1-restricted CD8+ CTL response, but with a reduced level of lysis against ovarian tumor cells. Dendritic cells loaded with SCCE 110-139 induced antigen-specific CD4+ T cell and CD8+ T cell responses. Although SCCE 110-139-loaded dendritic cells processed and presented the 123-131 epitope, the dominant CD8+ CTL response was directed against alternative epitopes within SCCE 110-139. CONCLUSIONS: The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15867247/Definition_of_an_immunogenic_region_within_the_ovarian_tumor_antigen_stratum_corneum_chymotryptic_enzyme_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15867247 DB - PRIME DP - Unbound Medicine ER -