B7-1 amplifies the response to interleukin-2-secreting tumor vaccines in vivo, but fails to induce a response by naive cells in vitro

Human Gene Therapy
S SalvadoriK Zier

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 cel...Continue Reading

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Jan 1, 1996·Springer Seminars in Immunopathology·H Chong, R G Vile
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