Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.

Chimeric antigen receptor (CAR)-T cell therapies represent a promising therapeutic approach for refractory autoimmune diseases. Although autologous CAR-T cells have achieved success thus far, they require expensive, individualised manufacturing, limiting their commercialisation potential. Allogeneic alternatives could overcome these scalability barriers, providing 'off-the-shelf' treatments, although they raise the issues of graft-vs-host reactions and host-mediated rejection. To mitigate such risks, gene-edited αβ T cells or non-alloreactive host cells (e.g., NK cells, γδ T cells) may be used. This review evaluates evidence of the functionality and commercial potential of various allogeneic CAR-T solutions for autoimmunity. Searches were conducted of PubMed, EMBASE and Web of Science to extract clinical and preclinical studies of allogeneic CAR-T cells, for the treatment of autoimmune diseases and B or T cell malignancies. In light of the paucity of data on autoimmune disease, the latter were included to facilitate extrapolation to the autoimmune setting. A total of 107 studies were included. The available clinical outcomes of efficacy and safety, as well as preclinical key findings, are reported. Current developments and potential future improvements for safety, effectiveness and cost-effective manufacture are then discussed. The findings of this review demonstrate the promising therapeutic potential of allogeneic CAR-T for autoimmune disease, with scope for the further optimisation of safety and scalable manufacture to facilitate commercialisation.