Table 2.

Site-specific antibody conjugations with non-cytotoxic compounds.

Categories of Payloads	MOA of Payload	Antibody Formats	Specific Site Used	Conjugation Chemistry	References
PEG	Prolonged serum half-life	Fab	Engineered Cys in C-terminus	Thiol-mediated conjugation	[57,58,59]
Antibiotics	Inhibitor of bacterial RNA polymerase	mAb	LC V205C	THIOMABTM	[60,61]
Immune-modulating compounds	PDE4 inhibitor for immune suppression	mAb	Unnatural amino acid	Oxime chemistry	[62]
	Liver LXR agonist for immune suppression	mAb	Unnatural amino acid	Oxime chemistry	[63]
	Agonist of glucocorticoid receptor	Nb	C-terminal LPETGG	Sortase A (SrtA) mediated transpeptidation	[64]
Protein degraders	PROTAC-mediated ERa and BRD4 degradation	mAb	Engineered Cys	THIOMABTM	[50]
	PROTAC-mediated BRD4 degradation	mAb	Hinge Cys	Click chemistry	[65]
		mAb	Engineered Cys	THIOMABTM	[51,52,66]
	LYTAC-mediated degradation through ASGPR	mAb	FGly in C-terminus of HC, hinge, CH1	Hydrazino-iso-Pictet–Spangler reaction and click chemistry	[67]
	LYTAC-mediated degradation through M6PR	mAb	N-glycans	Chemoenzymatic reaction	[68]
Ligand for proteins overexpressed in cancer	Chemically programmed bispecific Fab as T-cell engager (Fab-synthetic ligands)	Fab	Unnatural amino acid at HC K138	Oxime chemistry	[69]
		Fab	C-terminal Sec in HC	SeH-maleimide chemistry	[70]