Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases

Table 3 Mechanism of action of anti-tumor necrosis factor agents

Agent	Cell type	Mechanism of action	Ref.
ADA	CHO cell line stably expressing mTNF cocultured with human PBMCs	Induction of ADCC	[75]
ADA	CHO cell line stably expressing mTNF with human normal serum	Induction of CDC	[75]
IFX, ADA, ETA, Certo	TNF6.5 cells (murine NSO cell line stably expressing human TNF) with baby rabbit complement	CDC: IFX, ADA, ETA ++; Certo -	[50]
IFX, ADA, ETA, Certo	TNF6.5 cells in coculture with CD14-depleted PBMCs	ADCC: IFX, ADA ++, ETA+, Certo -	[50]
IFX, ADA, ETA, Certo	Peripheral blood lymphocytes	Apoptosis: IFX, ADA ++; ETA+, Certo -	[50]
IFX, ADA, ETA, Certo	Peripheral blood monocytes	Apoptosis: IFX, ADA ++; ETA+, Certo -	[50]
IFX, ADA	mTNF transfected cell line (SP2/0-11A5-1, murine)	Induction of CDC	[41]
IFX, ADA	Activated human PBMCs	No induction of CDC	[41]
GOL, ADA, IFX, Certo	mTNF expressing Jurkat cells with PBMCs/human serum	ADCC, CDC: GOL, ADA, IFX ++; ETA+, Certo-	[77]
ADA, IFX, GOL, Certo	mTNF expressing Jurkat cells	Apoptosis: ADA, IFX ++,	[77]
		GOL+, Certo+
ADA, IFX, ETA	cultured monocytes	Caspase-dependent apoptosis: ADA, IFX ++; ETA -	[53]
IFX, ETA	Peripheral blood lymphocytes and lamina propria T cells	Caspase-3 activation and apoptosis: IFX +; ETA -	[43]
ADA, IFX, ETA, Certo	Intestinal CD4/CD14 cells from IBD patients	Apoptosis by targeting mTNF/TNFR2: ADA, IFX, Certo +; ETA -	[24]

Apoptosis induction of anti-TNF agents. ++: Strong effect; +: Effect visible; -: No effect; ADA: Adalimumab; ETA: Etanercept; IFX: Infliximab; Certo: Certolizumab pegol; GOL: Golimumab; TNF: Tumor necrosis factor; mTNF: Membrane-bound TNF; sTNF: Soluble TNF; PBMCs: Peripheral blood mononuclear cells; ADCC: Antibody-dependent cellular cytotoxicity.