Table 1.

Comparison of CAR T cells and BiTEs

CAR T cellBiTE
StructureA synthetic gene construct encoding an scFv against tumor antigen linked to activation and costimulatory motifs.A recombinant protein composed of two linked scFvs; one binds to CD3 on T cells and the other to target a tumor antigen on tumor cells.
Effector cell typesEngineered CD8+ and CD4+ T cells (5). Less-differentiated subsets displaying better antitumor activity in vivo (TSCM and TCM; ref. 10).Endogenous CD8+ and CD4+ T cells (13). Antigen-experienced TEM but not TN effective (14).
Immune synapseAtypical (15).Typical (17–19).
Serial killingYes (16).Yes (22).
Killing mechanismsPerforin and granzyme B (16), Fas/Fas-L, or TNF/TNF-R.Perforin and granzyme B (17).
TraffickingActive. Trafficking of CAR T cells involves comprehensive interactions between various molecules and cell–cell interactions (57).Passive. Biodistribution depends on factors related to rates of diffusion through vascular endothelium, fluid flow rates, and interaction with target.
ToxicityCRS, neurotoxicity, B-cell aplasia (31, 49).CRS, neurotoxicity, B-cell aplasia (62, 64).
Clinical applicationsPretreatment lymphodepleting regime using cyclophosphamide and fludarabine.Premedicate with acetaminophen and an H1-antihistamine. One infusion.No lymphodepletion regime required. Premedicate with dexamethasone. Repeat administration necessary, including continuous i.v. infusion regimens.
FDA approvalYescarta was approved to treat adult patients with relapsed/refractory large B-cell lymphoma in 2017.Kymriah was approved to treat patients up to 25 years of age with refractory/relapsed B-ALL in 2017.Blinatumomab was approved to treat relapsed/refractory B-ALL in 2014 and 2017.
Other characteristicsIndividually produced for each patient.“Off the shelf” reagents.