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

ABSTRACT: The co-engagement of fragment crystallizable (Fc) gamma receptors (Fc?Rs) with the Fc region of recombinant immunoglobulin monoclonal antibodies (mAbs) and its contribution to therapeutic activity has been extensively studied. For example, Fc-Fc?R 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 Fc?R co-engagement on antigen-presenting cells (APCs). In the case of mAbs targeting CTLA-4 and TIGIT, the interaction with Fc?R on APCs enhanced antigen-specific T cell responses and tumoricidal activity. This mechanism extended to an anti-CD45RB mAb, which led to Fc?R-dependent regulatory T cell expansion in mice.

SUBMITTER: Waight JD 

PROVIDER: S-EPMC6292441 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature