Figure 1.

CD19 CAR T cell redirected killing of NHL cells. A. Structure of third generation of anti-CD19 CAR T cells including anti-CD19 single chain Ab fragment, spacer domain, transmembrane domain, T cell costimulatory domain (CD28) and T cell activation domain (CD3z). CD19 redirected CAR T cells induce apoptosis in sensitive NHL cells. B. Various potential mechanisms of the development of resistance by NHL cells to anti-CD19 CAR T cell-mediated apoptosis. These mechanisms may include: i: loos and/or down-regulation of the CD19 target antigen, ii: utilization of alternative B cell differentiation pathways, iii: altered dynamics of cell survival/anti-apoptotic signal transduction pathways, iv: altered expression profile of regulators of apoptosis, and v: physical barriers and immunosuppressive cytokines including TGF-b and IL-10. Please refer to the text for detailed information.