Intratumoral injection of interferon‐α and systemic delivery of agonist anti‐CD137 monoclonal antibodies synergize for immunotherapy

摘要: CD137 artificial costimulation results in complete tumor rejection several mouse models. Type I interferons (IFN) exert antitumor effects through an array of molecular functions on malignant cells, stroma and immune system cells. The fact that agonist anti-CD137 mAb induce regressions mice deficient the unique receptor for IFNs (IFNAR(-/-) ) indicated potential treatment combinations. Indeed, combination intratumor injections IFN-α intraperitoneal synergized as seen subcutaneous lesions derived from MC38 colon carcinoma, which is resistant to each if given separately. Therapeutic activity was achieved both against directly injected with distant concomitant tumors. Experiments bone marrow chimeras prepared IFNAR(-/-) WT concluded expression mainly required cells hematopoietic compartment. Synergistic correlated a remarkable cellular hyperplasia draining lymph nodes (TDLNs). Enlarged TDLNs contained more plasmacytoid conventional dendritic (DC) readily cross-presented. Importantly, numbers DC subtypes inversely size. Numbers CD8 T specific dominant antigen were increased at by separate but only slight augments due combination. Combined therapeutic strategy also TC-1 tumors established 24 days before onset. described realistic because (i) agents kind are clinically available (ii) equivalent procedures humans feasible.