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

• Published in: Cancer research (Chicago, Ill.) Vol. 57; no. 8; pp. 1561 - 1568
• Main Authors: YANG, S, DARROW, T. L, SEIGLER, H. F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.04.1997
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Genetic Vectors; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; HLA-A2 Antigen - metabolism; Humans; Immunophenotyping; Immunotherapy; Medical sciences; Melanoma - genetics; Melanoma - immunology; Mice; Pharmacology. Drug treatments; Skin Neoplasms - genetics; Skin Neoplasms - immunology; T-Lymphocytes, Cytotoxic - immunology; Transfection; Tumor Cells, Cultured; Antineoplastic agent; Human; HLA-System; Melanoma; Retroviridae; Cytotoxicity; In vitro; Allogeneic system; Adoptive transfer; Virus; Specificity; Immunotherapy; T-Lymphocyte; Tumor; Transduction; Gene therapy; Class I histocompatibility antigen; Tumor cell
• ISSN: 0008-5472; 1538-7445

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.