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Priming and activation of human ovarian and breast cancer-specific CD8+ T cells by polyvalent Listeria monocytogenes-based vaccines.
J Immunother ; 32(8): 856-69, 2009 Oct.
Article em En | MEDLINE | ID: mdl-19752748
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 DeltaactADeltainlB) as a vaccine vector. We present data that peptide-specific T cells recognize the human monocytic cell line THP-1 infected with recombinant Lm DeltaactADeltainlB 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 DeltaactADeltainlB encoding the epitopes. Our results demonstrate that live-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 an attractive strategy for active cancer immunotherapy in a clinical setting.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Neoplasias da Mama / Linfócitos T CD8-Positivos / Vacinas Anticâncer / Listeria monocytogenes Limite: Female / Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Neoplasias da Mama / Linfócitos T CD8-Positivos / Vacinas Anticâncer / Listeria monocytogenes Limite: Female / Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article