[PDF][PDF] FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis

R Dahan, E Sega, J Engelhardt, M Selby, AJ Korman… - Cancer cell, 2015 - cell.com
R Dahan, E Sega, J Engelhardt, M Selby, AJ Korman, JV Ravetch
Cancer cell, 2015cell.com
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 …
Summary
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.
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