Article: article from journal or magazin.
Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine.
Cancer immunity : a journal of the Academy of Cancer Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: epublish
The recent identification and molecular characterization of tumor-associated antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigen-derived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigen-expressing tumors and able to infiltrate antigen-containing peripheral sites.
Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cytotoxicity Tests, Immunologic, Drug Administration Schedule, Epitopes, T-Lymphocyte, Freund's Adjuvant, HLA-A2 Antigen, Humans, Injections, Subcutaneous, Lipids, Longitudinal Studies, Lymphocyte Activation, Melanoma, Membrane Proteins, Monophenol Monooxygenase, Neoplasm Proteins, Peptide Fragments, Proteins, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Uveal Neoplasms, Vaccines, Subunit
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