| Abstract: |
Parental and interleukin-2 (IL-2)-secreting CMS5 tumor cells were transfected with the B7-1 costimulatory molecule to amplify antitumor 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 antitumor 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. © 1995, Mary Ann Liebert, Inc. All rights reserved. |
| Keywords: |
controlled study; nonhuman; comparative study; cell proliferation; t-lymphocytes; animal cell; mouse; animal; mice; interleukin 2; spleen; cytotoxicity; tumor cells, cultured; transfection; mice, inbred balb c; fibrosarcoma; vaccines, synthetic; tumor cell; immunostimulation; tumor vaccine; cytokine release; tumor rejection; t lymphocyte activation; b7 antigen; interleukin-2; antigens, cd80; dna transfection; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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