Abstract
Genes encoding 2C T cell receptor (TCR) alpha, beta chains from H-2(b)-restricted L(d)-specific CD8(+) cells were successfully transduced into polyclonally activated CD8(+) cells by retroviral modification to generate antigen-specific cytotoxic T lymphocytes (CTL). Antigen-nonspecific CD8(+) T cells polyclonally expanded in the presence of interleukin (IL)-2, Th1 cytokines (interferon (IFN)-gamma and IL-12) and anti-IL-4 monoclonal antibody showed neither cytokine production nor cytotoxicity in response to L(d)-expressing P815 tumor cells. However, 2C-TCR gene-modified CD8(+) T cells exhibited both IFN-gamma production and cytotoxicity in response to P815 tumor cells. The antitumor activity of TCR gene-modified Tc1 cells was also demonstrated in vivo by Winn's assay. Thus, we have developed an efficient method to induce TCR gene-modified antigen-specific Tc1 cells that exhibit antitumor activity both in vitro and in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / virology
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Cell- and Tissue-Based Therapy
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Cytokines / metabolism
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / metabolism
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Genetic Therapy*
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Lymphoma / genetics
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Lymphoma / immunology
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Lymphoma / therapy*
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Mastocytoma / genetics
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Mastocytoma / immunology
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Mastocytoma / therapy*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell, alpha-beta / genetics*
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Receptors, Antigen, T-Cell, alpha-beta / isolation & purification
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Receptors, Antigen, T-Cell, alpha-beta / therapeutic use
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Retroviridae / genetics
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / pathology
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Tumor Cells, Cultured / transplantation
Substances
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Cytokines
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DNA-Binding Proteins
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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V(D)J recombination activating protein 2