CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help

CD40 is essential in enabling antigen-presenting cells to process and prese nt antigen effectively to T cells. We demonstrate here that when antibody a gainst CD40 is used to treat mice with syngeneic lymphoma, a rapid cytotoxi c T-cell response independent of T-helper cells occurs, with tenfold expans ion of CD8(+) T cells over a period of 5 days. This response eradicates the lymphoma and provides protection against tumor rechallenge without further antibody treatment. Thus, it seems that by treating mice with monoclonal a ntibody against CD40, we are immunizing against syngeneic tumors. The pheno menon proved reproducible with two antibodies against CD40 (3/23 and FGK-45 ) in three CD40(+) lymphomas (A20, A31 and BCL1) and gave partial protectio n in one of two CD40(-) lymphomas (EL4 and Ten1). Although the nature of th e target antigens on these lymphomas is unknown, CD8(+) T cells recovered f rom responding mice showed powerful cytotoxic activity against the target B -cell lymphoma in vitro.