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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 Cells¹

Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710

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.

¹ This work was supported in part by NIH Grants RO1-CA64949 and RO1-CA64959 and Department of Veterans Affairs Grant Seigler001 (to H. F. S).

² To whom requests for reprints should be addressed, at Department of Surgery, Box 3966, Duke University Medical Center, Durham, NC 27710.

Received 12/12/96. Accepted 3/ 5/97.

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