INTERLEUKIN-2-TRANSDUCED LYMPHOCYTES GROW IN AN AUTOCRINE FASHION ANDREMAIN RESPONSIVE TO ANTIGEN

The maintenance of T lymphocytes in vivo after adoptive transfer for i mmunotherapy requires the systemic administration of interleukin-2 (IL -2), but prolonged administration of IL-2 is associated with substanti al toxicity. The constitutive production of IL-2 by T cells may be an alternative method to prolong T-cell survival and potentially augment antitumor responses. To study the effects of constitutive production o f IL-2 on the growth and antigen reactivity of a murine T cell, the sp erm-whale myoglobin (SWM) specific T-cell line 14.1 was retrovirally t ransduced with the cDNA for IL-2. Cells that were transduced with vect ors without an internal promoter were able to proliferate in the absen ce of exogenously added IL-2, and to grow in an autocrine fashion. The se vectors used an internal ribosomal entry site (IRES) to allow trans lation of the neomycin phosphotransferase (neo') gene. In contrast, th e cells transduced with an IL-2 vector in which the neo' gene was unde r the transcriptional control of an internal SV-40 promoter failed to proliferate or grow in the absence of exogenously added IL-2. The prol iferation of the cells growing without IL-2 could be inhibited with an tibodies to the IL-2 receptor or to human IL-2, indicating that they w ere still IL-2 dependent. Despite their autocrine growth, no tumor for mation was observed in syngeneic mice injected subcutaneously with the transduced cells, and the cells retained their antigen reactivity and specificity. These results suggest that autocrine growth of T cells f or therapy will not interfere with effector function. (C) 1995 by The American Society of Hematology.