Abstract 3643: INCAGN1876, a unique GITR agonist antibody that facilitates GITR oligomerization

Abstract

Glucocorticoid-induced TNFR family related protein (GITR, CD357 or TNFRSF18) is a member of the tumor necrosis factor receptor superfamily (TNFRSF). Like other T cell co-stimulatory TNFR family members, GITR utilizes multiple oligomerization states to regulate the initiation of downstream signaling during T cell activation by antigen presenting cells (APCs). The formation of receptor superclusters, comprised of two or more trimeric molecules, has been defined for multiple TNFRs as a means of regulating downstream signal amplification. For co-stimulatory TNFRs, like GITR,

Multiple mechanisms for TRAF3-mediated regulation of the T cell costimulatory receptor GITR

“…In Treg, which have high levels of GITR expression, GITR signaling participates in regulation of proliferation and modulation of suppressive function ( 5 , 20 , 21 ). Targeting GITR via anti-GITR agonistic antibody ( 22 , 23 , 24 , 25 ), recombinant Fc-GITRL proteins ( 26 , 27 , 28 ), or engineered Chimeric Antigen Receptor T cells (CAR-T) expressing recombinant receptors with the GITR cytosolic domain ( 29 , 30 , 31 ) can exert potent therapeutic activities. However, GITR-mediated intracellular signaling remains only partially characterized.…”