Inhibitory IgG Receptor-Expressing Cells: The Must-Have Accessory for Anti-CD40 Immunomodulatory mAb Efficacy

Abstract

In this issue of Cancer Cell, Dahan and colleagues demonstrate that modified Fc regions of agonistic anti-human CD40 mAbs can drastically increase their efficiency in a mouse pre-clinical model expressing human CD40 and IgG receptors. This study also highlights the fine balance between increased treatment efficacy and secondary side effects.

CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir

“…FcγR represents a link between the humoral and cellular immune responses by triggering several functions, such as endocytosis and antibody-dependent cell-mediated cytotoxicity (ADCC) 13 . CD32a is a low-affinity Fc receptor with specificity for IgG antibodies and is commonly expressed on most myeloid cells, including monocytes, macrophages, and eosinophils 14 , 15 and is also expressed in natural killer (NK) cells and B-lymphocytes 16 , 17 . CD32 is highly regulated by agents such as phorbol 12-myristate 13-acetate (PMA) and cytokines, including interferon gamma (IFN-γ), dexamethasone and granulocyte-macrophage colony stimulatory factor (GM-CSF) 14 .…”

Role of Fc–FcγR interactions in the antitumor activity of therapeutic antibodies

“…Whether this observation will apply to other agonist antibodies remains to be determined. The mechanism underlying the superior agonism provided by binding selectively to FcγRIIB is unknown and could have multiple explanations, including cell type or location of FcγRIIB‐expressing cells or a direct cellular signaling component downstream of the various FcγR involved in crosslinking the CD40 signal 53 …”