Abstract 4059: Developing an allogeneic iPSC derived macrophage cell therapy for oncology

Abstract

The full potential of cell therapy has yet to be realized in solid tumor indications and new approaches are urgently required. Macrophages are innate immune cells that can kill tumor cells and orchestrate the anti-tumor immune response. Macrophage cell therapy is an exciting new approach to treat cancer with the aim to harness the powerful activity of macrophages to reignite the immune system. Patient derived macrophages, however, are difficult to genetically engineer and do not proliferate, which makes generating high-quality cells at clinically relevant scales challenging. To address this, we have developed an induced pluripotent stem cell (iPSC) approach to macrophage cell therapy. These cells can be genetically engineered at the iPSC stage and then differentiated into billions of highly functional iPSC derived macrophages (iMACs). This allogenic cell therapy product can then be cryopreserved and stored for immediate use in the clinic when the patient is ready. Here we show that iMACs function like normal macrophages. They migrate towards tumor cells, respond to challenges through innate immune receptors, and produce immune recruiting and activating cytokines and chemokines. iMACs also express high levels of antibody receptors and we show that these cells can be directed to kill tumors in vitro and in vivo via antibody dependent cellular phagocytosis. Furthermore, we have conducted a robust screen to develop a novel CAR that is optimized for use in iMACs. These receptors can be engineered into iMACs at the iPSC stage and trigger robust tumor cell killing. In summary, these data highlight the therapeutic potential of iMACs in oncology and support the further development of this technology for clinical use. Citation Format: Huafeng Wang, May Sumi, Christine Huh, Fereshteh Parviz, Jessica Mastroianni, Jane Healy, Nicole Stevens, Leah Mitchell, Susanne Lang, Dan Kaufman, Robert Hollingsworth, David T. Rodgers. Developing an allogeneic iPSC derived macrophage cell therapy for oncology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4059.