ANTIBODIES TO AN AUTOSTIMULATORY GROWTH-FACTOR (IL-2) OR ITS RECEPTORINDUCE DEATH OF LEUKEMOGENIC CELLS

We show for the first time that Ah-mediated antagonism of growth facto r activity can induce death of all cells in clonal populations survivi ng and growing by an autostimulatory mechanism. Models of autostimulat ory leukemia were generated by transfecting a mouse IL-2-dependent cel l line (FD,C/2) with vectors directing production of IL-2 by these cel ls. One series of clones grew in a density-dependent manner in the abs ence of exogenous IL-2 and produced tumors in syngeneic mice. Although these clones released relatively small amounts of IL-2, their growth and survival was only partially inhibited by Abs to IL-2 or the IL-2R, Another autostimulatory clone was derived, using a different vector, which produced significantly less IL-2. Treatment of cells of this clo ne with Abs to IL-2 or its receptor resulted in death of all cells. Th ese data demonstrate that Abs that antagonize growth factor action can induce the death of cells transformed by autostimulatory mechanisms, They suggest that while autostimulatory tumors are relatively resistan t to Abs that block growth factor action, this is a quantitative pheno menon, and competitive antagonists of growth factor action of sufficie ntly high affinity may provide effective and specific adjuvants to the treatment of such tumors.