期刊
JOURNAL OF IMMUNOTHERAPY
卷 32, 期 8, 页码 856-869出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e3181b0b125
关键词
ovarian and breast cancers; CD8(+) T-cell epitopes; recombinant Listeria monocytogenes; immune responses
资金
- NCI NIH HHS [15 R43 CA109868-02] Funding Source: Medline
Immunotherapeutic vaccine is potentially an effective strategy to combat cancer. Essential components of an effective vaccine must include antigens that are processed by the major histocompatibility complex class I pathway, presented by the tumor major histocompatibility complex molecules, and an effective antigen delivery platform that is capable of breaking self-tolerance. In this study, we characterized a set of ovarian cancer-specific T-cell epitopes delivered by live-attenuated recombinant Listeria monocytogenes (Lm Delta actA Delta inlB) as a vaccine vector. We present data that peptide-specific T cells recognize the human monocytic cell line THP-1 infected with recombinant Lm Delta actA Delta inlB encoding the epitopes. Furthermore, we demonstrate that recombinant L. monocytogenes (Lm)-infected antigen-presenting cells can prime and expand epitope-specific CD8(+) T cells in vitro and such CD8(+) T cells recognize not only peptide-loaded targets but also ovarian and breast tumor cells presenting endogenous epitopes. Finally, peptide-specific T cells generated using peripheral blood mononuclear cell from ovarian cancer patients recognize target cells infected with recombinant Lm Delta actA Delta inlB encoding the epitopes. Our results demonstrate that five-attenuated recombinant Lm can be used effectively as a vehicle to deliver cancer peptide antigens singly or as a multiepitope construct. Thus, the use of recombinant live-attenuated Lm strains encoding endogenously processed and presented tumor epitopes/ antigens represents all attractive strategy for active cancer immunotherapy in a clinical setting.
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