Table 1.

Comparison between CAR T-cells and T-cell recruiting bi-specific antibodies.

	CAR T-Cells	Bi-specific antibodies
Mechanism of action	- Direct cancer antigen recognition - Non MHC-restricted - Does not require pre-existing T cell infiltration, independent of receiver T cell characteristics	- Recruitment of immune effector T cells by their CD3 with another antigen expressed on the tumor cell - Non MHC-restricted - May be more dependent on quantity/quality of patients' T cells
Administration	- Single administration - Long half-life (months/years)	- Repeated administration (continuous infusion for non-IgG-like) - Short/intermediate half-life (hours/days)
Tissue penetration	- Homing of the T cells for blood, lymph nodes, and bone marrow	- Non IgG like: enhanced tissue penetration
Toxicity	- Acute reversible neurotoxicity (CD19) - Cytokine release syndrome (CRS)	- Lower toxicity expected - Acute reversible neurotoxicity (CD19) - Cytokine release syndrome (CRS)
Main diseases	- Outstanding activity in some hematological malignancies: B cell acute lymphoblastic leukemia, Diffuse Large B cell lymphoma (CD19) - Clinical trials in solid tumors	- B cell acute lymphoblastic leukemia (CD19) - Clinical trials for many solid tumors including colorectal, ovarian, breast and prostate cancer
Other limitations	- Clinical activity in solid tumors is still to demonstrate - Immunosuppressive microenvironment (rationale for combination with ICIs or use of optimized CAR T-cells) - Target specificity: risk of escape by loss of the target	- Clinical activity in solid tumors is still to demonstrate - Immunosuppressive microenvironment (rationale for combination with ICIs) - Target specificity: risk of escape by loss of the target
Cost and availability	- Long process, manufacturing issues - Cost+++	- Immediate availability, less manufacturing and regulatory issues - Cost+