Chimeric Antigen Receptor-T (CAR-T) Cells as “Living Drugs”: A Clinical Pharmacist Perspective

Figure 4

Challenges for CAR-T cell immunotherapy. CAR-T cell therapy is a complex treatment process. While outcomes are promising, there are associated challenges that must be addressed to assure continued success. (a) The efficacy and persistence of CAR-T cells in vivo is limited by the immunosuppressive TME, which impairs CAR-T cell function and reduces their anti-tumour effects. (b) CAR-T cell immunotherapy is associated with serious adverse effects such as cytokine release syndrome, neurotoxicity, anaphylaxis, and “on-target, off-tumour” toxicities. There are efforts in place to manage these toxicities and new CAR engineering strategies to offset these effects. (c) Expanding the therapeutic scope to solid tumours is needed to meet the unmet clinical need for treatment options for solid malignancies. There are many strategies being employed to overcome evasive solid tumour cells such as manipulation of CAR-T cell trafficking and combined TCR CAR-T profiles to limit antigen escape. (d) There is a significant logistical challenge associated with CAR-T cell therapy. Pharmacists are heavily involved in the logistical orchestration of this therapy from the leukapheresis process, to communicating with the other sites involved to coordinate timelines for instance. Key: IL-10 = interleukin 10, TGF-Β = transforming growth factor-Β, TAMs = tumour-associated macrophages, TANs = tumour-associated neutrophils, T_regs = regulatory T cells, MDSC = myeloid-derived suppressor cells, ROS = reactive oxygen species, PD1 = programmed cell death protein 1, scFv = single chain variable fragment, and TAA = tumour-associated antigen.