Induction of therapeutic T-cell immunity by tumor targeting with soluble recombinant B7-immunoglobulin costimulatory molecules

Tumor targeting with immunomodulatory molecules is an attractive strategy t o enhance the host's antitumor response. Expression of CD80 (B7-1) and CD86 (B7-2) costimulatory molecules in tumor cells has proven to be an efficien t may to enhance their immunogenicity, Here, we studied the effects of tumo r targeting with biotinylated recombinant soluble B7-1- and B7-2 immunoglob ulin G molecules (bio-B7-IgG) using a pretargeting approach based on the se quential use of a biotinylated antitumor monoclonal antibody and avidin; Mo use RMA T-lymphoma cells bearing either bio-B7-1-IgG or bio-B7-2-IgG on the ir surface prime in vitro naive CD8(+) CTLs, which are highly effective in adoptive immunotherapy, and induce therapeutic immunity when injected in tu mor-bearing animals. In vivo targeting of established RMA tumors with bio-B 7-IgG either cures tumor-bearing mice or significantly prolongs their survi val. The antitumor response induced by targeted bio-B7-IgG depends on both CD4(+) and CD8(+) T cells. Moreover, tumor targeting with bio-B7-IgG in viv o is critical for both expansion in lymphoid organs and mobilization into t he tumor of tumor-specific CD8(+) CTLs, When targeting is performed on poor ly immunogenic TS/A mammary adenocarcinoma, only bio-B7-1-IgG primes naive CTLs in vitro and cures or significantly prolongs the survival of tumor-bea ring mice in vivo, confirming that the two costimulatory molecules are not redundant with this tumor. Altogether, these data suggest that tumor avidin ation and targeting with soluble bio-B7-IgG may represent a promising strat egy to enhance the antitumor response in the host.