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). Antigen-specific clones have been utilized as tools for the investigation of factors important in mediating ACIT. 1. Characterization of the cellular immune response to retrovirus- induced leukemia. Tumor immunization promotes host HTL, CTL and suppressor cell immune responses. The majority of HTL are specific for viral envelope glycoprotein gp70, CTL recognize other tumor associated antigens (Ags) including gag. HTL produce interferon- gamma (IFN-gamma) and interleukin-2 (IL-2) after Ag stimulation, but are not directly cytolytic for tumor cells. In some cases, Ag- activated HTL transiently acquire the ability of 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 tumor cells. The intensity of DTH is sufficient to prevent tumor outgrowth without exogenous factors. The mechanism by which non- cytolytic HTL mediate tumor rejection is uncertain, but may include recruitment and activation of host macrophages or NK cells. Participation of specific host cells is being studied by depletion of host subpopulations with monoclonal antibodies (MoAb). 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. HTL remain activated after transfer, and can be distinguished from normal host lymphocytes on the basis of size and
