Io125 Is A Potent Inducer Of Tumor Immunogenicity

Combinatorial treatments with chemotherapeutics and immunotherapies are currently being investigated in several cancers. Chemotherapeutics can increase the immunogenicity of tumors besides modulating the immune system. Here we describe the development of a novel platinum-based therapeutic, IO-125, which assembles into stable nanoscale supramolecular structures. IO125 demonstrates enhanced activity compared with standard Pt drug across cancer lines. IO-125 preferentially targets tumors in vivo, and demonstrated improved efficacy in triple negative breast cancer (4T1), Lewis lung carcinoma (LLC) and melanoma (B16/F10) tumor models. Treatment with IO-125 elevates expression of immune-markers (including IGKC, PD-L1, PD-1, CD8A), which are associated with good prognosis. In addition, combinatorial treatment with IO-125 and antibody against immune checkpoint inhibitor(s) resulted in superior antitumor efficacy compared to treatment with antibody alone. This study shows that supramolecular therapeutics, especially IO125, can emerge as a novel approach to focally modulate the tumor immune contexture. Citation Format: Sanghamitra Mylavarapu, Shelly Kaushik, Yashpal Yadav, Monideepa Roy, Aniruddha Sengupta, Shiladitya Sengupta. IO125 is a potent inducer of tumor immunogenicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2231.