B7-1 Amplifies the Response to Interleukin-2-Secreting Tumor Vaccines In Vivo, but Fails to Induce a Response by Naive Cells In Vitro

Abstract

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. Parental and interleukin-2 (IL-2)-secreting tumor cells were transfected with the B7-1 costimulatory molecule. CMS5 cells transfected with B7-1 grew more slowly in vivo than parental CMS5 cells. Tumor cells secreting levels of IL-2 too low to cause rejection alone were rejected following transfection with B7-1. However, while neither B7-1⁺ nor IL-2-secreting, B7-1⁺ CMS5 cells stimulated naive spleen cells to proliferate or to become cytotoxic, restimulation of primed T cells by B7-1⁺ CMS5 cells resulted in stronger cytotoxicity responses than seen following restimulation by parental CMS5 cells. This suggests that costimulatory molecules can augment responses generated by IL-2-secreting tumor cells, but that the initiation of anti-tumor responses by naive T cells may depend upon antigen presentation by another cell. Thus, a major action of B7-1⁺ tumor cell vaccines might be to potentiate the responses of primed cells.