UNIQUE CHARACTERISTICS ASSOCIATED WITH SYSTEMIC ADOPTIVE IMMUNOTHERAPY OF EXPERIMENTAL INTRACEREBRAL TUMORS

Tumor-draining lymph node (LN) cells can be activated and expanded by stimulation with anti-CD3 followed by culture in interleukin-2 (IL-2) to acquire antitumor reactivity. Despite the lack of overt in vitro cy totoxicity, these effector cells mediate potent antitumor effects in t he adoptive immunotherapy of established visceral tumors. Recently, we further demonstrated the therapeutic efficacy of anti-CD3/IL-2-activa ted tumor-draining LN cells for the treatment of intracerebral tumors in a neutralization assay as well as by local and systemic adoptive tr ansfer. In this study, we analyzed the immunologic specificity, cellul ar requirements, and conditions that could promote the therapeutic eff ectiveness of the systemically transferred tumor-reactive cells. Using two antigenically distinct murine fibrosarcomas, MCA 205 and MCA 207, the adoptive immunotherapy of intracerebral tumors was immunologicall y specific, which was apparently determined by the tumor that stimulat ed the draining LN. Analysis of effector cells revealed the involvemen t of both CD4(+) and CD8(+) T cells for successful therapy. Therapeuti c efficacy of the transferred cells was greatly enhanced if the tumor- bearing host was also treated with sublethal whole-body irradiation (5 00 cGy). However, unlike the treatment of tumors located in visceral o rgans, the administration of exogenous IL-2 consistently inhibited the antitumor reactivity of the transferred cells against intracerebral t umors. These results demonstrate the feasibility of treating brain tum ors by systemic adoptive T-cell therapy, although the conditions for e fficient treatment appear to be different from those required for visc eral tumors.