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

RR French, HT Chan, AL Tutt, MJ Glennie - Nature medicine, 1999 - nature.com
RR French, HT Chan, AL Tutt, MJ Glennie
Nature medicine, 1999nature.com
CD40 is essential in enabling antigen-presenting cells to process and present antigen
effectively to T cells. We demonstrate here that when antibody against CD40 is used to treat
mice with syngeneic lymphoma, a rapid cytotoxic T-cell response independent of T-helper
cells occurs, with tenfold expansion 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 antibody against …
Abstract
CD40 is essential in enabling antigen-presenting cells to process and present antigen effectively to T cells. We demonstrate here that when antibody against CD40 is used to treat mice with syngeneic lymphoma, a rapid cytotoxic T-cell response independent of T-helper cells occurs, with tenfold expansion 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 antibody against CD40, we are immunizing against syngeneic tumors. The phenomenon proved reproducible with two antibodies against CD40 (3/23 and FGK-45) in three CD40+ lymphomas (A20, A31 and BCL 1) and gave partial protection in one of two CD40–lymphomas (EL4 and Ten1). Although the nature of the target antigens on these lymphomas is unknown, CD8+ T cells recovered from responding mice showed powerful cytotoxic activity against the target B-cell lymphoma in vitro.
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