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Table 1 Comparison between TCR-T, CAR-T, and CD3-directed bispecific antibodies and TCRs

From: T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors

  Modified TCR expressed on T-cells, NK cells, and other cells CAR expressed on T-cells, NK cells, and other cells CD3-directed bispecific antibodies and TCRs
Constructs Native or minimally engineered native TCR delivered via biologic vector Artificial receptor complex delivered by a biologic vector Antibody-like construct engineered for dual binding
Targets MHC peptides derived from intracellular proteins Surface proteins and glycans Either MHC peptides or surface proteins and glycans
Manufacturing Ex vivo gene transfer into autologous T-cells or NK cells, “personalized” for each patient Ex vivo gene transfer into autologous T-cells or NK cells, “personalized” for each patient “Off-the-shelf” conventional protein
Mechanism of action Binds and kills target cells leading to limited clonal expansion of T-cells Binds and kills target cells leading to extensive clonal expansion of T-cells Redirects endogenous T-cells to bind and kill target cells leading to polyclonal expansion of T-cells
Dosing Single or limited doses Single or limited doses Repetitive dosing
Availability Experimental basis only Experimental and commercially available products Experimental and commercially available products
Unique facets Small patient populations for any single construct Limited number of suitable potential targets Complex drug protein design needed to achieve optimal binding characteristics
Safety Modest cytokine release syndrome due to limited proliferation Extensive cytokine release syndrome due to extensive cell proliferation Cytokine release syndrome easily managed by adjusting dose and infusion rate
Mechanism of resistance Loss of target, loss of IFNγ signaling Loss of target, loss of IFNγ signaling Loss of target; loss of target fucosylation
  1. CAR chimeric antigen receptor, IFNγ interferon gamma, MHC major histocompatibility complex, NK natural killer, TCR T-cell receptors. References [20, 108]