Adoptive Chemoimmunotherapy of Murine Leukemia. Cytolytic T lymphocyte (CTL) and helper T lymphocyte (HTL) clones have been established from tumor-bearing mice and evaluated in models of adoptive chemoimmunotherapy (ACIT) of syngeneic murine leukemia (RBL5). Stable antigen-specific clones have been utilized as efficient tools for the investigation of factors important in mediating ACIT of established tumors. We hope to initiate human studies based on data obtained from the murine experimental models. Current Projects: 1. Characterization of the cellular immune response to retrovirus-induced leukemia. Tumor immunization promotes host HTL, CTL and suppressor cell immunes response. The majority of HTL are specific for the viral envelope glycoprotein gp70 while CTL recognize other tumor associated antigens (Ags). Non-activated HTL produce interferon- (IFN-) and interleukin-2 (IL-2) after Ag stimulation, but are not directly cytolytic for tumor cells. Recent studies have shown the Ag-stimulated HTL transiently acquire the ability to lyse tumor cells in vitro. 2. Activation, dissemination, and survival of HTL after adoptive transfer. HTL can be activated in situ to elicit a delayed-type hypersensitivity (DTH) reaction after local transfer with intact tumor cells. The intensity of DTH is sufficient to prevent tumor outgrowth without addition of exogenous factors. HTL can survive and expand in number after adoptive transfer if exogenous IL-2 and Ag are provided. Withdrawal of IL-2 is then associated with rapid reduction in cell numbers. Elimination of
