Generation of primary tumor-specific cytotoxic T lymphocytes from autologous and human lymphocyte antigen class I-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells.
Expression of B7.1 costimulatory molecules on tumor cells has been shown to elicit antitumor immunity in mice. In the present study, we have developed a human B7.1 retroviral vector system to effectively transduce human melanoma cell lines and investigated the potential role of B7.1 in the generation of tumor-specific CTLs from peripheral blood lymphocytes (PBLs) in vitro. We have demonstrated that B7.1-modified melanoma cells are able to induce primary CTL activity from autologous, human lymphocyte antigen (HLA) class I-matched allogeneic PBLs and purified CD8+ T cells in the absence of exogenous cytokines. CTLs generated by B7.1 are tumor specific and HLA class I restricted, and CD8+ T cells are primarily responsible for this specific cytotoxicity. Furthermore, CTLs generated from HLA class I-matched PBLs by B7.1 are cytolytic to tumor cells autologous to the stimulated PBLs. These data suggest that B7.1-modified tumor cells can be used as a potent tumor vaccine for both autologous and HLA class I-matched allogeneic patients.
Yang
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Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Darrow
T L
TL
Seigler
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HF
D000818:Animals; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I