Title: One platform endless pipelines:CAR-NK cells from engineered pluripotent stem cells using 3-D platform technology

Abstract

Clinical success of adoptive cell therapy with chimeric antigen receptor (CAR) T cells for treating hematological malignancies has revolutionized the field of cellular immunotherapy. However, critical to the success of CAR-engineered immune effector cell therapies will be the industrialization----converting the technologies into universal and cost-effective therapies for a large number of patients. Autologous CAR-T cell therapy faces two major obstacles: cell availability and high manufacturing cost, which makes it difficult for most patients. Donor-based CAR-T cells circumvent some of the above challenges, but still face the problem of graft versus host disease caused by allogenic T cells. Natural killer (NK) cell is a specialized immune effector cell type that recognizes and kills targets without human leukocyte antigen (HLA) restriction and prior sensitization. CAR-NK cells do not cause graft versus host disease (GvHD) and can be obtained from unrelated donors as well as pluripotent stem cells (PSC), representing an ideal off-the-shelf therapeutics for all patients. HebeCell has developed a robust proprietary scalable 3D-platform technology for PSC expansion and feeder-free NK cell differentiation with superior scalability and consistency compared to traditional approaches. As gene editing and CAR-engineering can be performed in PSCs, the establishment of master PSC-CAR cell bank targeting indication-specific antigens will provide inexhaustible cell sources for the manufacture of truly off-the-shelf and cost-effective CAR-NK cells for all patients of cancer, infectious and autoimmune diseases.The establishment of our proprietary 3D PSC-CAR-NK platform allows scalable, reproducible and efficient production of homogenous functional CAR-NK cells, which can be rapidly deployed worldwide for all patients.