. Author manuscript; available in PMC: 2016 Jul 1.

Published in final edited form as: Nat Rev Rheumatol. 2015 Dec 10;12(1):49–62. doi: 10.1038/nrrheum.2015.169

Table 3.

Next-generation selective inhibitors of soluble TNF-TNFR1 pathway

Class	Agent	Description
TNFR1-specific antibodies	ATROSAB^110,111	Full-length IgG against a specific epitope of TNFR1
		Maintains the conformation of TNFR1 in an inactive state and obstructs the binding of TNF and LTα
		The Fc-region has been mutated to abolish the capacity to bind Fcγ receptor and complement, avoiding immune system activation
	MDS5541 (REFS 109,112)	Domain-antibody comprising a single variable region with specificity for TNFR1 linked to another single variable region with specificity for albumin
	TROS¹¹³	Trivalent nanobody comprising two distinct domains with specificy for TNFR1 (resulting in high-affinity binding to TNFR1) and an anti-albumin domain
TNF muteins^114,115	XENP345 (REFS 145,146) and XPro1595 (REF. 147)	Dominant-negative TNF muteins that interact with native soluble TNF to form inactive heterotrimers, which have markedly reduced receptor-binding and signalling capacities
	R1antTNF^116,117	TNFR1-selective antagonistic TNF mutein, that is, selective binding capacity for TNFR1 without signalling capacity
	R1antTNF^116,117	Also has dominant negative TNF function, by forming inactive mixed heterotrimers with native TNF

Notes: TNF muteins are TNF molecules engineered to introduce amino acid changes; such modifications in the receptor interface domain can impair the receptor-binding and signalling capacity of these molecules. ATROSAB, antagonistic TNF receptor one-specific antibody; LT-α, lymphotoxin-α; R1antTNF, TNF receptor 1 antagonist; TNFR, TNF receptor; TROS, TNF receptor-one silencer.