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.
Salvadori
S
S
Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Gansbacher
B
B
Wernick
I
I
Tirelli
S
S
Zier
K
K
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000235:genetics
D018122:B7-1 Antigen; D007376:Interleukin-2; D014614:Vaccines, Synthetic