Table 2.

Comparison of main characteristics of bispecific antibodies versus CAR T-cell therapies.

Characteristics	Bispecific antibody	CAR T-cell therapy
Structure	Recombinant protein	Synthetic genetic construct
T-cell phenotype and effector function	Endogenous CD8+/CD4+ cells with higher cytotoxicity	Engineered naïve CD8+/CD4+ cells
Activation	CD3 signal 1 activation Newer generation may use co-stimulation	Signal 1 (CD3-ζ) and signal 2 (CD28, 4-1BB; in 2nd and 3rd generation CAR constructs), and more recently signal 3 (cytokine stimulation ex vivo)
Immune synapse	Typical	Atypical
Availability	“Off-the-shelf” – immediate use	3 to 5 weeks - In vitro manufacturing
Manufacturing failures and dosing variability	Not applicable	Manufacturing failure: < 10% cases Variability in terms of T-cell subset content, CAR transduction efficacy, and number of transfused CAR T-cells.
Dosing	Repetitive	Single (after lymphodepleting chemotherapy)
Administration	Inpatient and outpatient	Inpatient
Patient population	Can be used in elderly unfit patients	Cannot be used in frail and unfit patients
Cytokine Release Syndrome (Grade 3+)	0–1%	2–23%
ICANS	0%	1–28%
B-cell aplasia and cytopenia	B-cell aplasia recovers 6–18 months after last infusion Persistent cytopenia: rare	B-cell aplasia months to years after infusion. Cytopenia are common (15–95%) and often persist > 90 days (2–45%).
Applicability	Community practice	Specialized centers

ICANS Immune effector cell-associated neurotoxicity syndrome.