Table 1.

Immunotherapy based on the second signal blockage.

Molecule	Commercial name/clone	Target molecule	Mechanism of action	References
CTLA4-Ig	Abatacept/Belatacept	CD80/CD86	Competition for binding to B7 molecules on DC Upregulation of IDO enzyme expression High plasma levels of sHLA-G High secretion of immunomodulatory cytokines Inhibition of CD8+ T cells and NK cells Generation of Treg cells Inhibition of proliferation related to p27kip1 expression	[88, 107–123]
CTLA4-KDEL	—	CD80/CD86	Retention of costimulatory molecules within the ER T cell anergy by an IDO-independent way	[72, 115]
Anti-CD40L (CD154)/anti-CD40	3A8, 4D11, ASKP1240, 7E1	CD40/CD40L	Inhibition of antibody secretion Downregulation of T cell proliferation Inhibition of cytokine secretion and costimulatory molecule synthesis Upregulation of spleen IL-10+CD4+; T cells and downregulation of IFN-γ +CD4+ T cells	[117, 123–135]
PD-L1.Ig	—	PD-1/PD-1L	Suppression of T cell activation	[136–138]
Anti-TIM-1	RMT1-10	TIM-1	Blockage of TIM-1 ligation	[139–141]
Anti-OX40-L	—	OX40-OX40L interaction	Inhibition of OX40-OX40L signaling Prevention of T memory cells Reduction of effector T cells	[128, 129, 142, 143]
LFA3-Ig	Alefacept	LFA3 (CD58)	Depletion of CD8+ effector memory T cells Reduction of T cell activation	[113, 116, 144–146]