Antigen-independent tumor targeting by CBX-12 (alphalex-exatecan) induces long-term antitumor immunity.

To determine whether antigen-independent targeting of the TOP1 inhibitor exatecan to tumor with a pH-sensitive peptide (CBX-12) produces superior synergy with immunotherapy compared with unconjugated exatecan. and functional assays were performed via FACS and ELISA assays. efficacy was evaluated in the syngeneic CT26 model. CBX-12 combined with anti-PD-1 or anti-CTLA4 results in delayed tumor growth and complete response, with cured animals displaying long-term antitumor immunity. CBX-12 stimulates expression of MHC 1 and PD-L1 and is an inducer of immunogenic cell death, producing long-term immune recognition of tumor cells and resultant antitumor immunity. The authors' data provide the rationale for exploring immunotherapy combinations with CBX-12 in clinical trials.