An ER-Targeting Iridium(III) Complex which Induces Immunogenic Cell Death in Non-Small Cell Lung Cancer.

Immunogenic cell death (ICD) is a vital component of therapeutically induced anti-tumor immunity. An iridium(III) complex ( Ir1 ), containing an N , N -bis(2-chloroethyl)-azane derivate, as an endoplasmic reticulum-localized ICD inducer for non-small cell lung cancer (NSCLC) is herein reported. The characteristic discharge of damage-associated molecular patterns (DAMPs), i.e. cell surface exposure of calreticulin (CRT), extracellular exclusion of high mobility group box 1 (HMGB1) and ATP, were generated by Ir1 in A549 lung cancer cells, accompanied by an increase in endoplasmic reticulum stress and reactive oxygen species (ROS). The vaccination of immunocompetent mice with Ir1 -treated dying cells elicited an antitumor CD8 + T cell response and Foxp3 + T cell depletion, which eventually resulted in long-acting anti-tumor immunity by the activation of ICD in lung cancer cells. With the dual actions of ICD and chemotherapy against NSCLC, Ir1 has great potential as an antitumor agent. To the best of our knowledge, Ir1 is the first iridium-based complex that is capable of developing an immunomodulatory response by immunogenic cell death.