Fate Therapeutics brings first iPSC-derived CAR-T therapy to clinical development

August 12, 20200

Fate Therapeutics, a clinical stage biopharmaceutical company with a diverse pipeline of autologous and allogeneic cell therapies, received the IND clearance from US FDA for its FT819 CAR T-cell product candidate intended for the treatment of patients with relapsed or refractory B cell malignancies, including chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL), and non-Hodgkin lymphoma (NHL). The technology is spun out from Memorial Sloan Kettering with research led by Dr. Michel Sadelain. Fate holds an exclusive license covering the therapeutic application of the technology and intends to begin Phase 1 clinical trials soon.  

FT819 is a one-of-its-kind CAR-T therapy derived from induced pluripotent stem cells (iPSCs) and will be available as an off-the-shelf allogeneic CAR-T therapy targeting CD19+ malignancies. iPSCs are fully mature somatic cells that have been reprogrammed to revert to stem-cell state and have the potential to differentiate into any type of cell – essentially giving a renewable source of manufacturing CAR-T products. iPSC-derived CAR-T therapy provides promising advantages over the currently available autologous or donor derived CAR-T therapies – the most crucial being the ability to produce multiple doses from a single master clonal iPSC cell line, which substantially reduces the cost of production of the therapy, makes it scalable and overcomes logistical difficulties associated with donor derived CAR-T therapies.  

In addition to using a clonal master cell line, several other features have been introduced into the investigational therapy to improve the T-cell effector function, enable uniform CAR expression, enhance T-cell potency and prevent the occurrence of graft-vs-host disease (GvHD). Preclinical studies have demonstrated therapy specificity and its cancer-killing ability being comparable to that of autologous CAR-T therapies.  

Apart from Fate, companies like Allogene have allogeneic CAR-T products in clinical development, Takeda has a similar iPSC derived CAR-T product in preclinical development and plans to conduct clinical studies in 2021. The pace of development in CAR-T therapies is astounding, in a time-frame of less than 2 years, three autologous CAR-T products have entered the market and several others are in clinical pipeline. Off-the-shelf CAR-T therapy present the next frontier in the space and a remarkable scientific and technological revamp from the standard autologous CAR-T therapy. Allogeneic CAR-T therapy has the potential to negate one of the main concerns in the otherwise exciting landscape of regenerative medicine today. Scalability and widespread access remain a distant dream due to autologous nature of therapies and prohibitively high pricing. Fate’s therapy entering the clinic is a ray of hope that transformative care could potentially be a reality for wider patient pool and access concerns can be buried through scientific innovation.   

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