Table 1.
FcγR, FcRn and C1q binding profile of Fc-engineered variants of mAbs in clinical use or testing
| Fc variant | FcγRIIa | FcγRIIIa | FcγRIIb | C1q | FcRn | Example mAbs (antigen) | ||
|---|---|---|---|---|---|---|---|---|
| H131 | R131 | V158 | F158 | |||||
| N297A | – | – | – | – | – | – | ▪ | Atezolizumaba (PDL1), clazakizumab (IL-6), TRX518 (GITR) |
| L234A/L235A | – | – | – | – | – | – | ▪ | Spesolimab (IL-36R), teplizumab (CD37) |
| L234F/L325E/P331S | – | – | – | – | – | – | ▪ | Durvalumaba (PDL1), anifrolumab (IFNα/βR1) |
| Afucosylated | ▪ | ▪ | ↑↑ | ↑↑↑ | ▪ | ▪ | ▪ | Mogamulizumaba (CCR4), obinutuzumaba (CD20), benralizumaba (IL-5Rα), ublituximab (CD20), palivizumab-N (RSV), bemarituzumab (FGFR2b), cusatuzumab (CD70), gatipotuzumab (MUC1), ifabotuzumab (EPHA3) |
| M428L/N434S | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ↑↑ | VRC01LS (HIV), 10-1074-LS (HIV), 3BNC117-LS (HIV), PGT121.414.LS (HIV), VIR-2482 (influenza) |
| M252Y/S254T/T256E | ↓↓ | ↓↓ | ↓↓ | ↓↓ | ↓↓ | ▪ | ↑↑ | MEDI8897 (RSV), BOS161721 (IL-21), MEDI4893 (Staphylococcus aureus) |
| S239D/K274Q/Y296F/Y300F/L309V/I332E/A339T/V397M | ↑↑ | ↑↑ | ↑↑ | ↑↑↑ | ↑↑ | ? | ▪ | Tafasitamab (CD19), talacotuzumab (CD123) |
| P247I/A339Q | ? | ? | ↑↑ | ↑↑ | ? | ? | ? | Ocaratuzumab (CD20) |
| L235V/F243L/R292P/Y300L/P392L | ▪ | ↓ | ↑↑ | ↑↑ | ↓ | ↑↑ | ▪ | Margetuximab (HER2) |
| S267E | ▪ | ↑↑ | ↓ | ↓ | ↑↑ | ↑ | ▪ | APX005M (CD40) |
| S267E/L328F | ↓↓ | ↑↑↑ | – | – | ↑↑↑ | ↑ | ▪ | Obexelimab (CD19), XmAb7195 (IgE) |
| G237D/P238D/H268D/P271G/A330R | – | ↓ | – | – | ↑↑↑↑ | – | ▪ | 2141-V11 (CD40) |
| G236A/S239D/A330L/I332E/M428L/N434S | ↑↑↑ | ↑↑↑ | ↑↑ | ↑↑↑ | ↑ | – | ↑↑ | Elipovimab (HIV) |
| G236A/A330L/I332E/M428L/N434S | ↑↑ | ↑↑ | ↑↑ | ↑↑ | ↓ | – | ↑↑ | VIR-3434 (HBV) |
Note that the data for afucosylated Fc variants include data from mAbs enriched for afucosylated glycoforms and the binding affinities shown are dependent on the abundance of afucosylated glycoforms. –, no detectable binding; ▪, no change; ↓, reduced affinity compared with wild-type human IgG1; ↑, increased affinity compared with wild-type human IgG1; ?, no data available; CCR4, C-C chemokine receptor type 4; EPHA3, EPH receptor A3; FcγR, Fcγ receptor; FcRn, neonatal Fc receptor; FGFR2b, fibroblast growth factor receptor 2b; GITR, glucocorticoid-induced tumour necrosis factor; HBV, hepatitis B virus; HER2, human epidermal growth factor receptor (also known as ERBB2); IFNα/βR1, interferon-α/β receptor 1; MUC1, mucin 1; RSV, respiratory syncytial virus. aAntibodies in clinical use.