In vitro induction of cell-mediated immunity to murine leukemia cells - VI. Adoptive immunotherapy in combination with chemotherapy of leukemia in mice, using lymphocytes sensitized in vitro to leukemia cells

An adoptive chemoimmunotherapeutic model based on the use of chemotherapy and lymphocytes specifically sensitized against tumor cells in vitro was tested in mice transplanted with syngeneic leukemia cells. C57BL/6 and A strain mice were inoculated i.p. or i.v. (day 0) with lethal doses (1×10³-1×10⁵) of EL4 and YAC leukemia cells, respectively. Leukemic mice were subsequently treated (day 1 or day 3) with partially curative doses (80-140 mg/kg) of cyclophosphamide (Cy), followed by i.p. or i.v. administration of 1-3×10⁷ cytotoxic lymphocytes (CL) induced in macro-mixed leukocyte-tumor cell cultures (MLTC). The following results were obtained: untreated mice died with tumor within 20 days; mice receiving sensitized lymphocytes only showed a modest prolongation of survival and only 5-15% of the animals were cured; treatment with Cy alone or with Cy and normal lymphocytes prolonged survival considerably and cured 20-60% of the mice; mice subjected to Cy in conjunction with in vitro-sensitized lymphoid cells, either syngeneic or allogeneic, had survival rates of 80-100% (≥100 days). Under the conditions employed, no severe manifestations of clinical graft-versus-host (GVH) reaction were observed. These findings imply that in vitro-sensitized immunocytes and cytoreductive drugs can operate cumulatively.