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Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Waight JD,Chand D,Dietrich S,Gombos R,Horn T,Gonzalez AM,Manrique M,Swiech L,Morin B,Brittsan C,Tanne A,Akpeng B,Croker BA,Buell JS,Stein R,Savitsky DA,Wilson NS

doi

10.1016/j.ccell.2018.05.005

subject

Has Abstract

pub_date

2018-06-11 00:00:00

pages

1033-1047.e5

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(18)30219-8

journal_volume

33

pub_type

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