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Cancer Cell. 2015 Sep 14;28(3):285-95. doi: 10.1016/j.ccell.2015.08.004.

FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis.

Author information

1
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA.
2
Bristol-Myers Squibb, Biologics Discovery California, Redwood City, CA 94063, USA.
3
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA. Electronic address: ravetch@rockefeller.edu.

Erratum in

  • Cancer Cell. 2015 Oct 12;28(4):543.

Abstract

Immune checkpoint blockade of the programmed cell death protein 1 (PD-1) pathway by monoclonal antibodies (Abs) has shown promising clinical benefit in the treatment of multiple cancer types. We elucidated the contribution of the fragment crystallizable (Fc) domains of anti-PD-1 and anti-PD-ligand 1 (L1) Abs for their optimal anti-tumor activity. We revealed that distinct Fcγ receptor (FcγRs) dependency and mechanisms account for the in vivo activity of anti-PD-1 versus anti-PD-L1 Abs. Anti-PD-1 Abs were found to be FcγR independent in vivo; the presence of FcγR-binding capacity compromises their anti-tumor activity. In contrast, the anti-PD-L1 Abs show augmented anti-tumor activity when activating FcγR binding is introduced into the molecules, altering myeloid subsets within the tumor microenvironment.

PMID:
26373277
DOI:
10.1016/j.ccell.2015.08.004
[Indexed for MEDLINE]
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