S. Salvadori et al., B7-1 AMPLIFIES THE RESPONSE TO INTERLEUKIN-2-SECRETING TUMOR VACCINESIN-VIVO, BUT FAILS TO INDUCE A RESPONSE BY NAIVE CELLS IN-VITRO, Human gene therapy, 6(10), 1995, pp. 1299-1306
Parental and interleukin-2 (IL-2)-secreting CMS5 tumor cells were tran
sfected with the B7-1 costimulatory molecule to amplify anti-tumor res
ponses. 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 transfecti
on with B7-1. To determine whether the expression of B7-1 enabled the
tumor cells to activate T cells directly, their ability to stimulate i
n vitro functional responses by T cells was examined, We found that ne
ither B7-1(+) nor IL-2-secreting, B7-1(+) CMS5 cells stimulated naive
spleen cells to proliferate or to become cytotoxic. In contrast, resti
mulation of primed T cells by B7-1(+) CMS5 cells resulted in stronger
cytotoxicity responses than seen following restimulation by parental C
MS5 cells, Lysis was even higher if the B7-1(+) tumor cells also secre
ted IL-2. Our results suggest that the expression of costimulatory mol
ecules can augment responses generated by vaccinating with IL-2-secret
ing tumor cells, Furthermore, they are consistent with the hypothesis
that the initiation of an anti-tumor response by naive T cells may dep
end upon initial antigen presentation by another unidentified cell and
that the major action of IL-2-secreting and/or B7-1(+) tumor cell vac
cines might be to potentiate the response of already primed cells.