Modification of tumor cells by a low dose of Newcastle disease virus. Augmentation of the tumor-specific T cell response in the absence of an anti-viral response.
The present study elucidates the mechanism whereby viral xenogenization of highly metastatic ESb lymphoid tumor cells increases tumor immunogenicity and syngeneic tumor-specific T cell responses in comparison to nonmodified tumor cells. It was found that the frequency of cytotoxic T lymphocytes specific for the Esb tumor-associated transplantation antigen (TATA) and the cytotoxic anti-tumor activity in bulk cultures of immune spleen cells were significantly increased (by factor 3 and 25, respectively) when using virus-modified tumor cells. An amplified response was observed both in vivo and in vitro which might explain the demonstrated effectiveness of this approach for postoperative immunotherapy of ESb metastases. For the stimulation of tumor-specific cytolytic T lymphocytes (CTL) the ESb tumor cells which are highly metastatic were infected with an avirulent strain of the paramyxovirus Newcastle Disease Virus (NDV). Infection of ESb cells with low amounts of NDV was sufficient to lead to an increase in cytolytic activity of tumor-specific CTL after sensitization in vivo and restimulation in vitro. In a sensitive limiting dilution mixed leukocyte-tumor cell microculture system the direct effect of viral modification on the frequency and specificity of CTL was investigated. The number of ESb-specific CTL per spleen could be raised from about 3300 (without modification) to 9100 by both in vivo and in vitro application of ESb-NDV. One application of ESb-NDV (in vivo or in vitro) increased the number of CTL to 4900 and 4600, respectively. In split-type experiments it could be shown at the clonal level that viral modification did not alter the specificity of ESb-specific CTL.(ABSTRACT TRUNCATED AT 250 WORDS)
Von Hoegen
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P
Deutsches Krebsforschungszentrum, Institut für Immunologie und Genetik, Heidelberg, FRG.
Weber
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Schirrmacher
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V
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006649:Histocompatibility Antigens / Q000276:immunology*; D007111:Immunity, Cellular; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D009522:Newcastle disease virus / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen