Therapy of leukemia by nonimmune syngeneic spleen cells

In previous studies mice bearing an established transplanted syngeneic leukemia were cured by the adoptive transfer of immune lymphoid cells inoculated as an adjunct to chemotherapy, whereas nonimmune cells had no effect. By employing a smaller initial tumor inoculum to enhance the sensitivity of the chemoimmunotherapy model, the current study demonstrated that cells from normal nonimmune donors can also eradicate tumor. Thus, adult BALB/c mice given a lethal dose (1 x 10(4)) of LSTRA on day 0 were treated on day 5 with cyclophosphamide (CY) alone or CY plus nonimmune cells. Untreated mice all died by day 10. Cy alone prolonged median survival time (MST) to day 20, but all mice died. Treatment with CY plus 1 x 10(7) nonimmune cells prolonged the MST to day 26 and cured 16 of 48 mice. The effector cells, present in the spleens of normal and nude mice, were nonadherent lymphocytes resistant to anti Thy + C. These results are consistent with this effector cell in adoptive chemoimmunotherapy being an NK cell. However, they are distinct from classical NK cells since they are not directly cytotoxic in vitro in a short term CRA and do not neutralize tumor in vivo in a Winn assay.