B7-1 AMPLIFIES THE RESPONSE TO INTERLEUKIN-2-SECRETING TUMOR VACCINES IN-VIVO, BUT FAILS TO INDUCE A RESPONSE BY NAIVE CELLS IN-VITRO

Parental and interleukin-2 (IL-2)-secreting CMS5 tumor cells were transfected with the B7-1 costimulatory molecule to amplify anti-tumor responses. CMS5 cells transfected with B7-1 grew more slowly in vivo than did parental CMS5 cells. Moreover, tumor cells secreting levels of IL-2 too low to cause rejection alone were rejected following transfection with B7-1. To determine whether the expression of B7-1 enabled the tumor cells to activate T cells directly, their ability to stimulate in vitro functional responses by T cells was examined, We found that neither B7-1(+) nor IL-2-secreting, B7-1(+) CMS5 cells stimulated naive spleen cells to proliferate or to become cytotoxic. In contrast, restimulation of primed T cells by B7-1(+) CMS5 cells resulted in stronger cytotoxicity responses than seen following restimulation by parental CMS5 cells, Lysis was even higher if the B7-1(+) tumor cells also secreted IL-2. Our results suggest that the expression of costimulatory molecules can augment responses generated by vaccinating with IL-2-secreting tumor cells, Furthermore, they are consistent with the hypothesis that the initiation of an anti-tumor response by naive T cells may depend upon initial antigen presentation by another unidentified cell and that the major action of IL-2-secreting and/or B7-1(+) tumor cell vaccines might be to potentiate the response of already primed cells.