Doxorubicin combined with CpG for the Induction of Immunogenic Tumor Death and Antitumor Immune Responses

Optimal cancer therapy is one that results in complete eradication of all tumor cells by activating the host’s immune response against residual tumor cells following chemotherapy. However, most anticancer chemotherapeutic agents are immunosuppressive and induce non-immunogenic “silent” tumor cell death. Doxorubicin, on the other hand, belongs to the anthracycline family of chemotherapeutic drugs that have recently been shown to trigger immunogenic signals by dying tumor cells. The triggered “eat-me” signals (such as calreticulin, HMGB1, and ATP) facilitate the uptake of dying cells by antigen-presenting cells (APCs), Oligodeoxynucleotide with unmethylated C-G motifs (CpG ODN) is a powerful TLR9 agonist that has been shown to augment the ability of APCs to prime effective immune responses. Consequently, its combination with Doxorubicin presents an attractive approach to enhance tumor immunogenicity, ultimately resulting in the generation of potent antitumor antigen-specific responses.

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