H-2 restriction of adoptive immunotherapy of advanced tumors.

The purpose of this study was to determine if H-2 restriction of effector-target cell interactions is operative in vivo in the eradication of established tumors by adoptive immunotherapy. Models were developed for the treatment of disseminated parental strain FMR virus-induced tumors in CBF1 mice by adoptive chemoimmunotherapy (ACIT) in the form of noncurative tumoricidal chemotherapy followed by adoptively transferred immune CBF1 cells. The predominant effector cell in ACIT has been shown to be a T cell, which must be specifically immune to the tumor and capable of persisting in the host. Immune CBF1 cells were generated by secondary in vitro sensitization with parental strain FMR tumors of spleen cells from mice which had been primed in vivo by MSV inoculation to the cross-reactive FMR tumor antigens in the context of both parental haplotypes. FBL, an FMR tumor of C57BL/6 origin, and LSTRA, an FMR tumor of BALB/c origin, were used for sensitization in vitro and as targets in vivo in ACIT. Secondary sensitization with FBL rendered MSV-primed CBF1 cells more effective in ACIT of established FBL tumor but did not enhance the efficacy of MSV-primed cells in ACIT of LSTRA. Conversely, secondary sensitization with LSTRA rendered MSV-primed CBFi cells more effective in therapy of LSTRA but not FBL. The results demonstrate that enhancement of efficacy of immune cells in adoptive therapy of established tumors requires that the tumor cell used for in vitro sensitization and the tumor cell being treated in vivo share both tumor associated and H-2 antigens. Thus, tumor eradication in vivo by ACIT is H-2 restricted.