Figure 4.

Designs of approved TCEs. Brand names, INN, schematic structures, and design principles of approved TCEs. Smaller formats include scFv-based bispecific TCEs (BiTE) where two scFvs are joined in tandem. In Kimmtrak (tebentafusp), the tumor antigen-binding scFv is replaced by a soluble TCR (sTCR) (Liddy et al., 2012; Lowe et al., 2019). In Imdelltra (tarlatamab), a BiTE is fused to a Fc moiety for half-life extension. Larger formats are usually asymmetric 1:1-format mAbs where one Fab arm binds a tumor antigen and the other Fab arm binds CD3. Columvi (glofitamab) is a 2:1-format mAb where one Fab arm binds the tumor antigen (CD20) and the other arm contains two fused Fab fragments. The proximal Fab binds CD3, whereas the distal Fab binds CD20. This format increases the avidity for CD20. BCMA, B cell maturation antigen, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17); CD19, cluster of differentiation 19; CD20, cluster of differentiation 20; Fc, fragment crystallizable; gp100, glycoprotein 100, also known as premelanosome protein (PMEL); GPRC5D, G protein–coupled receptor family C group 5 member D; HLA, human leukocyte antigen; scFv, single-chain fragment variable.

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