| Added by | pmartino |
|---|---|
| Group name | EquipePM |
| Item Type | Journal Article |
| Title | Fc-engineered monoclonal antibodies to reduce off-target liver uptake |
| Creator | Mangeat et al. |
| Author | Tristan Mangeat |
| Author | Matthieu Gracia |
| Author | Alexandre Pichard |
| Author | Sophie Poty |
| Author | Pierre Martineau |
| Author | Bruno Robert |
| Author | Emmanuel Deshayes |
| Abstract | BACKGROUND: Radiolabeled-antibodies usually display non-specific liver accumulation that may impair image analysis and antibody biodistribution. Here, we investigated whether Fc silencing influenced antibody biodistribution. We compared recombinant 89Zr-labeled antibodies (human IgG1 against different targets) with wild-type Fc and with mutated Fc (LALAPG triple mutation to prevent binding to Fc gamma receptors; Fc?R). After antibody injection in mice harboring xenografts of different tumor cell lines or of immortalized human myoblasts, we analyzed antibody biodistribution by PET-CT and conventional biodistribution analysis. RESULTS: Accumulation in liver was strongly reduced and tumor-specific targeting was increased for the antibodies with mutated Fc compared with wild-type Fc. CONCLUSION: Antibodies with reduced binding to Fc?R display lower liver accumulation and better tumor-to-liver ratios. These findings need to be taken into account to improve antibody-based theragnostic approaches. |
| Publication | EJNMMI research |
| Volume | 13 |
| Issue | 1 |
| Pages | 81 |
| Date | 2023-09-11 |
| Journal Abbr | EJNMMI Res |
| Language | eng |
| DOI | 10.1186/s13550-023-01030-0 |
| ISSN | 2191-219X |
| Library Catalog | PubMed |
| Extra | PMID: 37697076 PMCID: PMC10495296 |
| Tags | bnif, Fc, Fc gamma receptor, first-last-corresponding, ipam, LALAPG mutation, ligue, mabimprove, Off-target, original, PET-CT, ram, siric, top |
| Date Added | 2023/11/03 - 09:56:41 |
| Date Modified | 2023/11/20 - 14:54:54 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
