| Literature DB >> 29894690 |
Jeremy D Waight1, Dhan Chand1, Sylvia Dietrich2, Randi Gombos1, Thomas Horn1, Ana M Gonzalez1, Mariana Manrique1, Lukasz Swiech1, Benjamin Morin1, Christine Brittsan1, Antoine Tanne1, Belinda Akpeng1, Ben A Croker3, Jennifer S Buell1, Robert Stein1, David A Savitsky4, Nicholas S Wilson5.
Abstract
The co-engagement of fragment crystallizable (Fc) gamma receptors (FcγRs) with the Fc region of recombinant immunoglobulin monoclonal antibodies (mAbs) and its contribution to therapeutic activity has been extensively studied. For example, Fc-FcγR interactions have been shown to be important for mAb-directed effector cell activities, as well as mAb-dependent forward signaling into target cells via receptor clustering. Here we identify a function of mAbs targeting T cell-expressed antigens that involves FcγR co-engagement on antigen-presenting cells (APCs). In the case of mAbs targeting CTLA-4 and TIGIT, the interaction with FcγR on APCs enhanced antigen-specific T cell responses and tumoricidal activity. This mechanism extended to an anti-CD45RB mAb, which led to FcγR-dependent regulatory T cell expansion in mice.Entities:
Keywords: CD45RB; CTLA-4; Fc engineering; Fcγ receptor; TCR signaling; TIGIT; cancer immunotherapy; effector T cells; immune synapse; regulatory T cells
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Year: 2018 PMID： 29894690 PMCID： PMC6292441 DOI： 10.1016/j.ccell.2018.05.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743