Figure 2.

Proposed mechanism of action of TX200-TR101. HLA-A^∗02-CAR-Tregs are expected to migrate into the HLA-A^∗02-positive allograft tissue (1), where they will interact with their target antigen HLA-A^∗02 (2), leading to their activation and proliferation (3, 4). On the basis of the known mechanism of action of Tregs,⁶ HLA-A^∗02-CAR-Tregs are then expected to exert a variety of immunomodulatory functions to dampen effector and cytotoxic T cell activation (5, 7) responsible for transplant rejection. Through the production of immunomodulatory cytokines, HLA-A^∗02-CAR-Tregs are expected to modulate the activation of Teff (5) and antigen-presenting cells. Moreover, the interaction of activated HLA-A^∗02-CAR-Tregs with antigen-presenting cells should lead to the creation of an unfavorable microenvironment for the Teff, leading to their apoptosis (6). HLA-A^∗02-CAR-Tregs might also have a cytolytic activity and induce the apoptosis of Teff (7). Moreover, the HLA-A^∗02-CAR-Tregs may suppress B-cell activation and differentiation into antibody-producing cells, reducing the risk of antibody-dependent cellular cytotoxicity directed against the transplanted tissue (not depicted). CAR, chimeric antigen receptor; DC, dendritic cell; HLA-A^∗02, human leukocyte antigen class I molecule A^∗02; Teff, effector T cell; Tregs, regulatory T cells.