Table 1.
Therapeutic applications and opportunities derived from FcRn-based biology.
| FcRn-based therapeutic approaches | Mode of action | Therapeutic use | Reference |
|---|---|---|---|
| TRANSPORTING IgG | |||
| Respiratory epithelium | Transcytosis of IgG across respiratory epithelium | Non-invasive pulmonary delivery of IgG-based therapeutics in non-human primates and humans | (8, 44, 46–48) |
| Vaccination against respiratory pathogens | |||
| Intestinal epithelium | Transcytosis of IgG across intestinal epithelium | Providing passive and active immunity against enteric pathogens and infections | (31, 34, 35, 58) |
| Transepithelial transport of Fc-targeted nanoparticles | Enabling drugs currently limited by low bioavailability to be efficiently delivered through oral administration | ||
| Genitourinary epithelium | Transcytosis of IgG across genitourinary epithelium | Providing passive and active immunity against infections with genitourinary entrance | (55, 56) |
| Placenta | Transcytosis of IgG across the placenta from mother to fetus | Providing passive immunity to fetus | (51–53, 59–61) |
| Transplacental delivery of IgG-based therapeutics | |||
| REGULATING IgG HALF-LIFE | |||
| Extending serum half-life of IgG and IgG-based therapeutics by augmenting FcRn interactions | Increasing FcRn binding with selective mutations within the IgG Fc fragment that enable pH-dependent binding of IgG | Increasing bioavailability of IgG- and IgG-based therapeutics in serum and tissue, effectiveness shown for | (42, 62, 63, 65, 64, 66) |
| Prolonging factor VIII and IX serum half-life for hemophilia treatment | |||
| Enhanced anti-tumor activity | |||
| Protection against (S)HIV | |||
| Increasing FcRn binding to multimeric IgG containing immune complexes | Increasing and inducing MHC I and MHC II antigen presentation | (21, 31, 34, 36, 37, 67) | |
| Increasing and inducing antigen-specific T-cell responses | |||
| Relevance and effectiveness shown for | |||
| Tumor protection at mucosal sites (intestines, lung) | |||
| Vaccination with tumor antigen for increased anti-tumor surveillance | |||
| Reducing serum half-life of IgG- and IgG-based therapeutics | IVIG effect and saturating FcRn binding | Amelioration of IgG-mediated diseases such as Immune thrombocytopenic purpura Myasthenia gravis | (15, 19, 68–78) |
| Peptide mimetics or anti-FcRn antibodies that block IgG binding | |||
| Engineered antibodies with higher FcRn affinity that enhance IgG degradation (Abdegs) | |||
| Colitis | |||
| Arthritis | |||
| Pemphigus vulgaris | |||
| Autoimmune encephalomyelitis | |||
| Lupus nephritis | |||