{
  "id": 5653341,
  "title": "Antibodies with Engineered Fc Domains Having Absolute Binding Selectivity to either FcγRIIa or FcγRI Delineate the Respective Effector Phenotypes by Human Monocytes and Macrophages",
  "url": "https://urgent.news/2026/09/04/antibodies-with-engineered-fc-domains-having-absolute-binding",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-04T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748147v1?rss=1"
  },
  "original_language": "en",
  "account": "Human immune complexes, such as IgG1, bind to all Fc{gamma} receptors (Fc{gamma}R) found on myeloid cells, making it difficult to discern the specific role each Fc{gamma}R plays in Fc effector functions. Researchers have now engineered an Fc2KG, a Fc domain of aglycosylated human IgG1 that binds with near physiological affinity to Fc{gamma}RIIa/b without binding to any other Fc{gamma}Rs. Crystallographic analysis revealed how mutations within the Fc domain compensate for the absence of N297 glycan and allow for selective binding. Single-cell phagocytosis assays demonstrated that particles opsonized with Fc-engineered antibodies formatted with Fc2KG or an Fc domain that only binds Fc{gamma}RI are ingested by THP-1 cells at nearly identical rates. Furthermore, CD16+ primary human monocytes show that selective Fc{gamma}RII engagement is a key contributor to ADCP mediated by wild-type IgG1. Additionally, Fc2KG formatted antibodies induce high levels of GM-CSF. When tested on M1-like monocyte-derived human macrophages, trastuzumab formatted with wild-type IgG1 Fc, Fc2KG, or Fc5 demonstrated equal proficiency in trogocytotic killing of SK-BR-3 HER2+ cells. However, only Fc{gamma}RI engagement led to the secretion of proinflammatory cytokines. These findings indicate that precisely engineered Fc antibodies can be utilized to elucidate the precise effector functions of human Fc{gamma}Rs, which is crucial for optimizing therapeutic antibodies.",
  "summary": "IgG1 immune complexes bind to all the Fc{gamma} receptors (Fc{gamma}R) expressed on myeloid cells, making it challenging to determine the precise role of each Fc{gamma}R on Fc effector phenotypes. Here we report the engineering of Fc2KG, an aglycosylated human IgG1 Fc domain that binds with near physiological affinity to Fc{gamma}RIIa/b with no detectable binding to any other Fc{gamma}Rs.…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}