Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens
| Autor: | Rachel H. McMahan, Kimberly R. Jordan, Jill E. Slansky, John W. Kappler, Charles B. Kemmler |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Cytotoxicity
Immunologic T-Lymphocytes Receptors Antigen T-Cell Mice Transgenic Spodoptera Major histocompatibility complex Cancer Vaccines Cell Line Interferon-gamma Mice Antigen Antigens Neoplasm Peptide Library Cell Line Tumor Cytotoxic T cell Animals Peptide library Mice Inbred BALB C Multidisciplinary biology Immunodominant Epitopes Histocompatibility Antigens Class I Vaccination MHC restriction Biological Sciences Tumor antigen Cell culture Immunology Vaccines Subunit biology.protein Female Clone (B-cell biology) Colorectal Neoplasms |
| Popis: | Peptide vaccines enhance the response of T cells toward tumor antigens and represent a strategy to augment antigen-independent immunotherapies of cancer. However, peptide vaccines that include native tumor antigens rarely prevent tumor growth. We have assembled a set of peptide variants for a mouse-colon tumor model to determine how to improve T-cell responses. These peptides have similar affinity for MHC molecules, but differ in the affinity of the peptide-MHC/T-cell receptor interaction with a tumor-specific T-cell clone. We systematically demonstrated that effective antitumor responses are generated after vaccination with variant peptides that stimulate the largest proportion of endogenous T cells specific for the native tumor antigen. Importantly, we found some variant peptides that strongly stimulated a specific T-cell clone in vitro, but elicited fewer tumor-specific T cells in vivo, and were not protective. The T cells expanded by the effective vaccines responded to the wild-type antigen by making cytokines and killing target cells, whereas most of the T cells expanded by the ineffective vaccines only responded to the peptide variants. We conclude that peptide-variant vaccines are most effective when the peptides react with a large responsive part of the tumor-specific T-cell repertoire. |
| Databáze: | OpenAIRE |
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