Locust Walk Breakthrough Innovation Reports: Oncology IPS-Effector Cell Therapies

In this report you can find an overview and analysis of the following:

• The CAR-T and oncology cell therapy landscape has broadly seen significant continued development, with over 2,000 therapies in development and ~1,350 active trials globally
• Though most development has been in standard CAR-T, the landscape has broadened to include gamma delta T-, NK-, macrophage, and TIL therapies, with NK cell therapies seeing particularly widespread development
• Following the approval of 5 autologous therapies, establishing safe and effective off-the-shelf solutions remains a significant interest to offer readily accessible and economical therapies for more patients
• iPS-derived therapies have many advantages that may position them as a ‘best in class’ off-the-shelf cell source including enabling consistent gene editing, a more homogenous products, and superior scalability
• However, iPS technologies face unique challenges, including complex differentiation and CMC protocols, proving ‘bioequivalent’ efficacy to native cell types while avoiding immune rejection, and lack of tumorigenicity from undifferentiated PSCs
• Most development has focused on iPS-derived NK (iNK) cell therapies, led by Fate Therapeutics, as there are efficient and established differentiation protocols to achieve highly active iNK cells that mirror the natural NK phenotype
• In contrast, efforts to produce T-phenotype (iT) cells achieve similar or better activity to standard CAR-T remains a challenge. However, there remains strong interest in developing iT and other cell types, mirroring the broader cell therapy field
• Fate’s iNK and Brightpath’s iPS-derived NKT (iNKT) have entered the clinic. Fate’s FT596 CD-19 CAR-iNK program has released interim data showing promising response rates, though there are questions around its durability
• Several key players are following these companies, including Century, Astellas, Cartherics, and Cytovia among others