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. Author manuscript; available in PMC: 2024 Dec 1.
Published in final edited form as: Nat Rev Cancer. 2024 May 13;24(6):399–426. doi: 10.1038/s41568-024-00690-x

Table 2 ∣.

Bispecific antibodies approved or nearing approval by the FDA and EMA

Target Antibody Structure Format Major indications Adverse effects
T cell engagers
CD19xCD3 Blinatumomab graphic file with name nihms-1998788-t0007.jpg Lacks Fc (short half-life ~2 h)
~54 kDa
B cell precursor ALL CRS
Neurotoxicity
Infection
Cytopenia
TLS
CD20xCD3 Mosunetuzumab graphic file with name nihms-1998788-t0008.jpg IgG1 Fc (half-life extension)
N297G mutation (aglycosylation and reduced ADCC)
~146 kDa
Lymphoma CRS
Neurotoxicity
Infection
Cytopenia
Embryo–fetal toxicity
Epcoritamab graphic file with name nihms-1998788-t0009.jpg IgG1 Fc (half-life extension)
L234F, L235E, D265A mutation (reduced ADCC)
~146 kDa
Lymphoma CRS
Neurotoxicity
Infection
Cytopenia
TLS
Glofitamab graphic file with name nihms-1998788-t0010.jpg Two anti-CD20 scFvs linked with one anti-CD3 scFv
IgG1 Fc (half-life extension)
P329G, L234A, L235A mutation (reduced ADCC)
~194 kDa
Lymphoma CRS
Neurotoxicity
Infection
Cytopenia
Imvotamab (in clinical trial) graphic file with name nihms-1998788-t0011.jpg IgM pentamer (ten CD20-binding sites)
Albumin fusion (half-life extension)
~960 kDa
Lymphoma CRS
Cytopenia
Hypophosphatemia
BCMAxCD3 Teclistamab graphic file with name nihms-1998788-t0012.jpg IgG4 Fc (half-life extension)
S228P (hinge stabilization), and F234A and L235A mutation (reduced FcγR binding)
~143 kDa
Multiple myeloma CRS
Neurotoxicity
Infection
Cytopenia
Hepatotoxicity
Embryo–fetal toxicity
Elranatamab graphic file with name nihms-1998788-t0013.jpg IgG2 Fc (half-life extension)
~145 kDa
Multiple myeloma CRS
Neurotoxicity
Cytopenia
GPRC5DxCD3 Talquetamab graphic file with name nihms-1998788-t0014.jpg IgG4 Fc (half-life extension)
S228P (hinge stabilization), and F234A and L235A mutation (reduced FcγR binding)
~147 kDa
Multiple myeloma CRS
Neurotoxicity
Cytopenia
Skin rash
Hepatotoxicity
Embryo–fetal toxicity
GP100xCD3 Tebentafusp graphic file with name nihms-1998788-t0015.jpg Lacks Fc, MW above renal filtration cut-off (half-life 6–8 h)
~75–77 kDa
Melanoma CRS
Skin rash
Hepatotoxicity
Embryo–fetal toxicity
Receptor blockers
EGFRxcMET Amivantamab graphic file with name nihms-1998788-t0016.jpg IgG1 (half-life extension)
Fc afucosylation (enhanced ADCC)
K409R, F405L mutation (for Fab exchange)
~146 kDa
Lung cancer Skin rash
Stomatitis
Muscle pain
Cytopenia
Electrolyte abnormality
Embryo–fetal toxicity
Her2xHer2 Zanidatamab (in clinical trial) graphic file with name nihms-1998788-t0017.jpg Two anti-HER2 scFvs (bind two distinct HER2 epitopes)
IgG1 (half-life extension)
~125 kDa
HER2+ cancers Diarrhoea
Infusion reaction
Cardiac failure
PD1xCTLA4 Volrustomig MEDI5752 (in clinical trial) graphic file with name nihms-1998788-t0018.jpg IgG1 (half-life extension)
L234F, L235E, P331S mutation (reduced FcγR binding)
~145 kDa (estimated)
Multiple solid tumours Checkpoint inhibitor-associated irAEs:
Diarrhoea
Thyroid disorders
Skin rash
Hepatotoxicity

ADCC, antibody-dependent cellular cytotoxicity; ALL, acute lymphoblastic leukaemia; CRS, cytokine release syndrome; Ig, immunoglobulin; irAEs, immune-related adverse events; IV, intravenous; kDa, kilodalton; scFv, single-chain variable fragment; TLS, tumour lysis syndrome. Fc-bearing bispecific antibodies also carry Fc mutations that enable pairing of the heterogenous heavy chains (not shown).