14676632

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Successful immunotherapy with peptide vaccines depends on the in vivo generation of sufficient numbers of anti-tumor T cells with appropriate phenotypic and functional characteristics to mediate tumor destruction. Herein, we report the induction of high frequencies of circulating CD8+ T cells (4.8% to 38.1%) directed against the native gp100:209-217 peptide derived from the gp100 melanoma-melanocyte tumor antigen in five HLA-A*0201 patients at high risk of recurrence of melanoma after multiple courses of immunization with modified gp100:209-217(210M) peptide in IFA. Longitudinal peripheral blood mononuclear cell (PBMC) analysis revealed a phenotypic shift of native peptide-specific CD8+ T cells from an early effector to an effector memory (CD27- CD28- CD62L- CD45RO+) phenotype with repeated immunizations and functional maturation that correlated with gp100:209-217 peptide-specific T-cell precursor frequencies. Postimmunization PBMC exhibited direct ex vivo recognition of melanoma cell lines in ELISPOT analysis, showed lytic capability against peptide-pulsed target cells, and proliferated in response to native peptide stimulation. One year after final immunization, circulating vaccine-specific CD8+ T cells persisted in patients' PBMC with a maintained effector memory phenotype. The results herein demonstrate the efficacy of a multiple course peptide-immunization strategy for the generation of high frequencies of tumor antigen-specific T cells in vivo, and further show that continued peptide immunization results in the escalating generation of functionally mature, tumor-reactive effector memory CD8+ T lymphocytes.

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http://linkedlifedata.com/resource/pubmed/journal/9706083

http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A*02:01 antigen, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A Antigens, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SILV protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, Subunit, http://linkedlifedata.com/resource/pubmed/chemical/gp100 Melanoma Antigen

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pubmed-meshheading:14676632-Adult, pubmed-meshheading:14676632-Aged, pubmed-meshheading:14676632-CD8-Positive T-Lymphocytes, pubmed-meshheading:14676632-Cancer Vaccines, pubmed-meshheading:14676632-Cell Differentiation, pubmed-meshheading:14676632-Cytotoxicity Tests, Immunologic, pubmed-meshheading:14676632-Dose-Response Relationship, Immunologic, pubmed-meshheading:14676632-HLA-A Antigens, pubmed-meshheading:14676632-HLA-A2 Antigen, pubmed-meshheading:14676632-Humans, pubmed-meshheading:14676632-Lymphocyte Count, pubmed-meshheading:14676632-Melanoma, pubmed-meshheading:14676632-Membrane Glycoproteins, pubmed-meshheading:14676632-Middle Aged, pubmed-meshheading:14676632-Neoplasm Proteins, pubmed-meshheading:14676632-Phenotype, pubmed-meshheading:14676632-Vaccination, pubmed-meshheading:14676632-Vaccines, Subunit, pubmed-meshheading:14676632-gp100 Melanoma Antigen

Surgery Branch, National Cancer Institutes of Health, Bethesda, MD 20892, USA.