In vitro induction of cell-mediated immunity to murine leukemia cells - V. Adoptive immunotherapy of leukemia in mice with lymphocytes sensitized in vitro to leukemia cells

The present study was undertaken to evaluate the feasibility of adoptive immunotherapy of murine leukemias using lymphocytes specifically sensitized in vitro to leukemia cells (EL4, YAC). Large numbers of activated lymphocytes of both syngeneic and allogeneic origin were generated in macro-mixed leukocyte-tumor cell cultures (MLTC) and their antitumor reactivity was assessed in vitro (⁵¹Cr release assay) and in vivo (Winn neutralization assay and immunotherapy of established leukemia). In the Winn assay, tumor-lymphocyte mixtures were administered by subcutaneous (s.c.), intraperitoneal (i.p.), or intravenous (i.v.) routes. Sensitized lymphocytes were highly effective in inhibiting tumor growth when given by the s.c. route, whereas they were much less so following administration by the other routes. There was a good correlation between the cytotoxic potential in vitro and the tumor-neutralizing capacity in vivo. Syngeneic lymphocytes were more efficient than were allogeneic lymphocytes. In the immunotherapy experiments, cytotoxic lymphocytes (CL) were inoculated by different routes 24-48 h after mice had been given a lethal dose of tumor cells. Although a significant retardation of tumor growth was achieved, complete cures were rare. These findings thus demonstrate that, under the conditions employed, CL generated in vitro and endowed in vitro with strong antitumor cytotoxicity have, by themselves, only a limited immunotherapeutic capacity in vivo.