Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes

Figures & data

Table 1 Approaches of pDNA vaccination for reestablishing β cell tolerance

Approach	Transgene	Efficacy at blocking β cell autoimmunity
		Preclinical		Clinical
		Early	Late
Chemokine Neutralization	CCL4	+64
	CXCL10	+63
Cytokine-induced Treg	IL-4	+65
	IL-10	+66
	IL-4 + IL-10	+128
	TGFβ1		+70
Cytokine Neutralization	IFNγR-Ig	+71
β cell autoantigen-induced Treg	Intracellular GAD65	+83,129,130	+129
	Secreted GAD65	+83
	GAD65IgFc		+60
	Insulin B chain	+73,74
	Proinsulin		+75
	HSP60		+77
Combined pDNA vaccination	Intracellular GAD65 + IL-4		+80
	GAD65IgFc + IL-4		+67
	GAD65IgFc + IL-10		+68	+69
	GAD65IgFc + IL-4 + IL-10		+68	+69
	GAD65-Proinsulin fusion + mCD80	+81
	Proinsulin + mCD80	+131
	Secreted GAD65 + BAX		+132
	GAD65 (intracellular) + NMαCD3			+125
	Proinsulin + αCD40L	+76

Table 2 Viral-based vectors primarily used in the treatment of Type 1 diabetes

Viral vector	Approach	Ex vivo islet transduction	i.p./i.v./i.m. delivery	In vivo pancreas transduction
			Transgene
Adenovirus
	Antigen:	N.D.	proinsulin133	N.D.
	Immune modulating cytokines:	TGFβ134,135	TGFβ135,136	N.D.
		TNFα137
		IL-12p40137,138
		IL-4139	IL-4140
		IL-10139
		Indoleamine 2,3-dioxygenase141	N.D.	N.D.
		IL-1Rα142–144
	Pro-inflammatory modulators:	vascular endothelial growth factor142,144
		hepatocyte growth factor143
		human Fas ligand145,146
		insulin-like growth factor 1147
	Co-stimulatory blockade:	CTLA-4134	N.D.	N.D.
		CTLA-4Ig134,137
rAAV
	Antigen:	N.D.	GAD95,96	N.D.
		N.D.	preproinsulin97	N.D.
	Immune modulating cytokines:	IL-4148	IL-498	IL-4116
		IL-10100	IL-1098–101,149,150	IL-10116
	Pro-inflammatory modulators:	N.D.	HO-1103	glucagon-like peptide 1117
			AAT102	IκB116
	Co-stimulatory blockade:	N.D.	N.D.	N.D.
Lentivirus
	Antigen:	N.D.	proinsulin151	N.D.
	Immune modulating cytokines:	IL-4152	N.D.	N.D.
		TGFβ134
		thioredoxin153	N.D.	N.D.
	Pro-inflammatory modulators:	IL-1Rα154
		cFLIP155
	Co-stimulatory blockade:	CTLA-4Ig134	N.D.	N.D.
		CTLA-4134

N. D., Not Determined.

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