Allogeneic Chimeric Antigen Receptor Therapy in Lymphoma

Abstract

The therapeutic armamentarium has significantly expanded since the approval of various CD19-targeting chimeric antigen receptor T cell (CAR-T) therapies in non-Hodgkin lymphoma (NHL). These CAR-Ts are patient-specific and require a complex, resource, and time-consuming process. While this appears promising, autologous CAR-Ts are limited due to the lack of accessibility, manufacturing delays, and variable product quality. To overcome these, allogeneic (allo) CARs from healthy donors appear appealing. These can be immediately available as "off the shelf" ready-to-use products of standardized and superior quality exempt from the effects of an immunosuppressive tumor microenvironment and prior treatments, and potentially with lower healthcare utilization using industrialized scale production. Allogeneic CARs, however, are not devoid of complications and require genomic editing, especially with αβ T cells to avoid graft versus host disease (GvHD) and allo-rejection by the recipient's immune system. Tools for genomic editing such as TALEN and CRISPR provide promise to develop truly "off the shelf" universal CARs and further advance the field of cellular immunotherapy. Several allogeneic CARs are currently in early phase clinical trials, and preliminary data is encouraging. Longer follow-up is required to truly assess the feasibility and safety of these techniques in the patients. This review focuses on the strategies for developing allogeneic CARs along with cell sources and clinical experience thus far in lymphoma.

Keywords: Allogeneic CAR-T; CAR-T; Non-Hodgkin lymphoma.

Fig. 1

Various allogeneic CARs with genomic editing techniques (abbreviations: CAR, chimeric antigen receptor; TAA, tumor associated antigen; B2M, β2 microglobulin; Ab, antibody; TCR, T cell receptor; FasL, Fas ligand; iPSC, induced pluripotent stem cells; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; IL, interleukin; NKG2D, natural killer group 2 member D).