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