Combined anti-CD40 and anti-IL-23 monoclonal antibody therapy effectively suppresses tumor growth and metastases
Menée à l'aide de modèles murins, cette étude suggère l'intérêt de combiner des anticorps monoclonaux anti-CD40 et anti-IL23 pour lutter contre la croissance d'une tumeur primitive et de métastases pulmonaires
Tumor-induced immunosuppression remains one of the major obstacles to many potentially effective cancer therapies and vaccines. Host IL-23 suppresses the immune response during tumor initiation, growth and metastases, and neutralization of IL-23 causes IL-12-dependent anti-tumor effects. Here we report that combining agonistic anti-CD40 mAbs to drive IL-12 production, and anti-IL-23 mAbs to counter the tumor promoting effects of IL-23, has greater anti-tumor activity than either agent alone. This increased anti-tumor efficacy was observed in several experimental and spontaneous lung metastases models as well as in models of de novo carcinogenesis. The combination effects were dependent on host IL-12, perforin, IFNy, NK and/or T cells and independent of host B cells and IFNaB sensitivity. Interestingly, in the experimental lung metastases tumor models, we observed that intracellular IL-23 production was specifically restricted to MHC-IIhiCD11c+CD11b+ cells. Further, an increased in proportion of these IL-23 producing cells were detected only in tumor models where IL-23 neutralization was therapeutic. Overall, these data suggest the clinical potential of using anti-CD40 (push) and anti-IL-23 mAbs (pull) to tip the IL-12/23 balance in established tumors.