T-cell–engaging bispecific antibodies in clinical development
| Bispecific antibody . | Target . | Format . | Valency . | Route of administration . | Properties . |
|---|---|---|---|---|---|
| Teclistamab (JNJ-640079957) | BCMA × CD3 | IgG4 duobody | Monovalent CD3 binding Monovalent BCMA binding | Subcutaneous | Fc mutated ↑ half-life, and ↓ immunologic effector function–mediating CRS |
| Elranatamab (PF-06863135) | BCMA × CD3 | IgG2a BsAb | Monovalent CD3 binding Monovalent BCMA binding | Subcutaneous | Fc mutated ↑ half-life, heterodimerization, and ↓ immunologic effector function–mediating CRS |
| TNB-383B (ABBV-383) | BCMA × CD3 | IgG4 BsAb | Low-affinity CD3 binding Bivalent BCMA binding | Intravenous | Decouples T-cell activation from CRS and activates Teff over Tregs |
| Linvoseltamab (REGN5458) | BCMA × CD3 | IgG4 BsAb | Monovalent CD3 binding Monovalent BCMA binding | Intravenous | Fully human, VelociBi™ Fc silent region, mutation in protein A binding site |
| Alnuctamab (CC-93269) | BCMA × CD3 | IgG1 BsAb, asymmetrical 2 + 1 format | Monovalent CD3 binding Bivalent BCMA binding | Intravenous/ subcutaneous | Heterodimeric mutated Fc with intact FcRn, and ↓ immunologic effector function–mediating CRS |
| Talquetamab (JNJ-64407564) | GPRC5D × CD3 | IgG4 duobody | Monovalent CD3 binding Monovalent GPRC5D binding | Subcutaneous | Fc-mutated ↑ half-life, and ↓ immunologic effector function–mediating CRS |
| Forimtamig RG6234 (RO7425781) | GPRC5D × CD3 | IgG1, asymmetrical 2 + 1 format | Monovlent CD3 binding Bivalent GPRC5D binding | Intravenous/ subcutaneous | Fc-mutated (silent Fc) ↑ half-life |
| Cevostamab (BFCR4350A) | FcRL5 × CD3 | Humanized IgG1-based Ab | Monovalent CD3 binding Monovalent FcRL5 binding | Intravenous | FcRL5 expressed on B and plasma cells |
| Bispecific antibody . | Target . | Format . | Valency . | Route of administration . | Properties . |
|---|---|---|---|---|---|
| Teclistamab (JNJ-640079957) | BCMA × CD3 | IgG4 duobody | Monovalent CD3 binding Monovalent BCMA binding | Subcutaneous | Fc mutated ↑ half-life, and ↓ immunologic effector function–mediating CRS |
| Elranatamab (PF-06863135) | BCMA × CD3 | IgG2a BsAb | Monovalent CD3 binding Monovalent BCMA binding | Subcutaneous | Fc mutated ↑ half-life, heterodimerization, and ↓ immunologic effector function–mediating CRS |
| TNB-383B (ABBV-383) | BCMA × CD3 | IgG4 BsAb | Low-affinity CD3 binding Bivalent BCMA binding | Intravenous | Decouples T-cell activation from CRS and activates Teff over Tregs |
| Linvoseltamab (REGN5458) | BCMA × CD3 | IgG4 BsAb | Monovalent CD3 binding Monovalent BCMA binding | Intravenous | Fully human, VelociBi™ Fc silent region, mutation in protein A binding site |
| Alnuctamab (CC-93269) | BCMA × CD3 | IgG1 BsAb, asymmetrical 2 + 1 format | Monovalent CD3 binding Bivalent BCMA binding | Intravenous/ subcutaneous | Heterodimeric mutated Fc with intact FcRn, and ↓ immunologic effector function–mediating CRS |
| Talquetamab (JNJ-64407564) | GPRC5D × CD3 | IgG4 duobody | Monovalent CD3 binding Monovalent GPRC5D binding | Subcutaneous | Fc-mutated ↑ half-life, and ↓ immunologic effector function–mediating CRS |
| Forimtamig RG6234 (RO7425781) | GPRC5D × CD3 | IgG1, asymmetrical 2 + 1 format | Monovlent CD3 binding Bivalent GPRC5D binding | Intravenous/ subcutaneous | Fc-mutated (silent Fc) ↑ half-life |
| Cevostamab (BFCR4350A) | FcRL5 × CD3 | Humanized IgG1-based Ab | Monovalent CD3 binding Monovalent FcRL5 binding | Intravenous | FcRL5 expressed on B and plasma cells |
BCMA, B-cell maturation antigen; CD3, cluster of differentiation 3; CRS, cytokine release syndrome; FcRL5, fragment crystallizable receptor-like 5 (FcRL5) also referred to as FcRH5; GPRC5D, G protein–coupled receptor, class C, group 5.