ONLINE COVER Glycoengineering the Tip of the Spear. This month’s cover depicts cellular soldiers (blue myeloid cells at the left and green T cells at the right) rushing to battle cancer cells. Leading the charge is an Fc-enhanced form of an anti–PD-L1 checkpoint blockade antibody. Using mice humanized to express human Fcγ receptors (FcγRs), Saban et al. found that the in vivo antitumor activity of anti–PD-L1 antibodies was enhanced by removing fucose residues from glycans on the human IgG1 Fc region to promote binding to activating FcγRs on myeloid cells. Treatment with afucosylated anti–PD-L1 enabled depletion of immunosuppressive PD-L1+ cells in the tumor microenvironment and blocked inhibitory signaling in PD-1+ T cells. These findings suggest that modifications in the Fc scaffold of currently used anti–PD-L1 immunotherapy drugs could yield a boost in their antitumor activity.
Credit: Marzia MunafòScience Immunology
- Volume 8|
- Issue 81|
- Mar 2023
ONLINE COVER Glycoengineering the Tip of the Spear. This month’s cover depicts cellular soldiers (blue myeloid cells at the left and green T cells at the right) rushing to battle cancer cells. Leading the charge is an Fc-enhanced form of an anti–PD-L1 checkpoint blockade antibody. Using mice humanized to express human Fcγ receptors (FcγRs), Saban et al. found that the in vivo antitumor activity of anti–PD-L1 antibodies was enhanced by removing fucose residues from glycans on the human IgG1 Fc region to promote binding to activating FcγRs on myeloid cells. Treatment with afucosylated anti–PD-L1 enabled depletion of immunosuppressive PD-L1+ cells in the tumor microenvironment and blocked inhibitory signaling in PD-1+ T cells. These findings suggest that modifications in the Fc scaffold of currently used anti–PD-L1 immunotherapy drugs could yield a boost in their antitumor activity.
Credit: Marzia Munafò
