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Promise and pitfalls of allogeneic chimeric antigen receptor therapy in plasma cell and lymphoid malignancies

Chimeric antigen receptor (CAR) T‐cell therapy is a promising immunotherapy in haematological malignancies. However, the currently approved products are generated from autologous T cells that require orchestration of several logistically complex steps, which include patient eligibility, apheresis capability, complex manufacturing processes and shipping logistics. Use of third‐party donor‐derived (allogeneic) effector cells that allows the generation of ‘off‐the‐shelf” CAR T cells (allo‐CAR) could circumvent many of the problems associated with autologous CAR T‐cell therapy. Several allogeneic products are entering clinical trials, and though early, the results look promising. The recognised potential benefits of allo‐CAR do not come without significant challenges, that must be overcome for their widespread use. Alloreactivity, i.e. graft‐versus‐host disease (GVHD), and rejection of donor T cells is one of the major barriers, while other potential barriers include immunogenicity, unknown in vivo persistence, and CAR T‐cell yield. In the present review, we provide a comprehensive review of the challenges associated with autologous CAR, the benefits and potential challenges associated with allo‐CAR. Finally, we review the available platforms for allo‐CAR for B‐cell and plasma cell malignancies.