fig2

Figure 2. Schematic representation of the main mechanisms of resistance to TCR therapy. Mutation or downregulation of the target antigen led to resistance due to failed recognition of the myeloma cells from the T cells. High tumor burden and high levels of soluble antigen can reduce the efficacy of bispecific antibodies by trapping them before they can reach the target cell. Shedding of the antigen from the target cell to the effectory cell can cause trogocytosis, leading to fratricide of the T cells. Immune exhaustion and an immunosuppressive microenvironment also contribute to disease resistance. For detailed explanations of T cell redirecting therapy mechanisms of resistance, see the main text. TCR: T cell redirecting; MHC I: Major histocompatibility complex class I.