Abstract
Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens. Based on our prior genome-wide interrogation of human prostate cancer tissues to identify genes over-expressed in cancer and absent in the periphery, we targeted SIM2 as a prototype autologous tumor antigen for these studies. Using humanized transgenic mice we found that the 9aa HLA-A*0201 epitope, SIM2(237-245), was effective at inducing an antigen specific response against SIM2-expressing prostate cancer cell line, PC3. Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2(237-245) epitope, and an IL-2 response by CD4 T cells to the SIM2(240-254) epitope. This peptide was also effective at inducing CD8+ T-cells that responded specifically to SIM2-expressing tumor cells. Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigen Presentation / immunology
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / immunology
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Basic Helix-Loop-Helix Transcription Factors / chemistry
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / immunology*
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cancer Vaccines / immunology
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Cell Line
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Cytokines / biosynthesis
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Epitopes, T-Lymphocyte / chemistry
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Epitopes, T-Lymphocyte / immunology*
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Gene Expression
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Gene Expression Profiling
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HLA-A2 Antigen / immunology
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Histocompatibility Antigens Class I / immunology*
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Histocompatibility Antigens Class II / immunology*
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Humans
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Immunization
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Immunotherapy
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Male
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Mice
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Mice, Transgenic
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / metabolism
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Neoplasms / therapy
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Peptides / chemistry
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Peptides / immunology*
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Spleen / cytology
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Spleen / immunology
Substances
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Antigens, Neoplasm
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Basic Helix-Loop-Helix Transcription Factors
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Cancer Vaccines
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Cytokines
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Epitopes, T-Lymphocyte
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HLA-A*02:01 antigen
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HLA-A2 Antigen
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Peptides
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SIM2 protein, human