Abstract 3203: EVO cells Oncology: Tailored genetic engineering of iPSC-derived immune effector cells and combination with the right biologic therapeutics result in optimal killing of primary tumor cells from patients

Current autologous cell therapies, with blockbuster products on the market, have been leading for a decade to unprecedented clinical successes in patients with hematological malignancies. However, these patient-derived T-cell therapies are facing many challenges. The use of GMP iPSC lines to produce immune effector cells will reduce the complexity of the manufacturing process and will provide an unlimited source of starting material. The goal of the EVOcells Oncology platform is to offer a truly allogeneic cell therapy platform to treat a broad number of cancer patients with consistent quality and scalability of the final product. Besides, the versatility of our platform to produce different immune cell types combined to customized genetic engineering strategies will bring cell therapy to the level of personalized medicine. Our “off-the-shelf” cell therapy platform has already validated two pillars: iPSC-derived NK cells (iNK) and iPSC-derived Macrophages (iMACs). Through multiple genetic engineering strategies specific to each immune cell type, we are developing a comprehensive portfolio of cell therapy products to address specific tumor escape mechanism in liquid and solid tumors. Our initial effort aimed to develop these two innate immune cell types to propose efficacious cell therapies with an increased safety profile as they have low risk of graft-versus-host disease (GvHD) or CRS (Cytokine Release Syndrome). Thanks to the expression of a broad pattern of activatory receptors, iNK cells form Immunological Synapses with tumor cells leading in turn to efficient killing with and without addition of a CAR construct. Besides, we demonstrated the possibility to combine “naked” iNK cells with marketed therapeutic monoclonal antibodies (mAb) to further improve their efficacy. At the end of the differentiation process, iMACs are showing a M0 like phenotype with high plasticity allowing the in vitro differentiation of the cells towards either a M1 or a M2 polarization in response to the appropriate stimulations. iMACs produce key macrophages cytokines and are able to kill tumor cells via ADCP (Antibody-Dependent-Cell-Phagocytosis) mechanism when combined to a therapeutic mAb. Thanks to our collaboration with clinicians at the IUCT-Oncopole (Toulouse Cancer Hospital), we were able to identify appropriate cancer indications and further demonstrate in a translational fashion that both iNK and iMACs are able to kill primary resistant tumor cells which were isolated