Highly Efficacious Allogeneic CAR-MAIT Cells Targeting Solid Tumors

CAR-T therapy has shown great success in hematologic malignancies. However, its efficacy in solid tumors remains limited. Furthermore, shifting from an autologous to allogeneic products is crucial for making this therapy accessible and affordable.

Mucosal-associated invariant T-(MAIT) cells have unique qualities that make them ideal candidates for allogeneic cell products targeting solid tumors. MAIT cells possess a semi-invariant T cell receptor, which virtually eliminates the risk of graft-versus-host disease-(GvHD). Additionally, their tissue-resident nature suggests they may have superior migratory capabilities to solid tumors.

Pluri has developed a novel three-dimensional bioreactor platform that mimics physiological conditions and maximizes MAIT cell growth. This system consistently yields highly functional, proliferative MAIT cells in clinically relevant numbers. In-depth transcriptomic and membranomic profiling of placental MAIT cells reveals a unique expression profile distinct from conventional T cells. Real-time chemotaxis assay has confirmed superior migration of MAIT cells compared to T cells toward chemokine gradients and tumor cell supernatants, addressing a key barrier in solid tumor targeting.

Incorporating tumor-specific CARs in MAIT cells has shown efficacy and polyfunctionality of resulting cells in response to diverse tumor targets. Pluri’s CAR-MAIT cells have demonstrated potent and sustained anti-tumor activity in serial rechallenge and 3D killing assays.

In summary, Pluri’s MAIT cells address key limitations of existing T and NK cell therapies. CAR-MAIT cells provide a compelling solution for targeting solid tumors, combining effective migration with robust anti-tumor activity and persistence. Our scalable platform supports the clinical realization of MAIT cell-based therapies, opening new possibilities for treating solid cancers.