Anti-CD40 antibody induces antitumor and antimetastatic effects: The role of NK cells

We assessed the effect of the stimulatory anti-CD40 Ab on NK cell activatio n in vivo and the therapeutic potential of activated NK cells in tumor-bear ing mice. Single-dose i.p. injection of the anti-CD40 Ab resulted in produc tion of IL-12 and IFN-gamma in vivo, followed by a dramatic increase in NK cell cytolytic activity in PBLs, NK cell activation by anti-CD40 Ab was als o observed in CD40 ligand knockout mice. Because NK cells express CD40 liga nd but not CD40, our results suggest that NK activation is mediated by incr eased cytokine production upon CD40 ligation of APCs. Treatment of tumor-be aring mice with anti-CD40 Ab resulted in substantial antitumor and antimeta static effects in three tumor models. Depletion of NK cells with anti-asial o GM1 Ab reduced or abrogated the observed antitumor effects in all the tes ted models. These results indicate that a stimulatory CD40 Ab indirectly ac tivates NK cells, which can produce significant antitumor and antimetastati c effects.