| Added by | JPPOUGET |
|---|---|
| Group name | EquipeJPP |
| 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 | Number: 1 PMID: 37697076 PMCID: PMC10495296 |
| Tags | Fc, Fc gamma receptor, first-last-coresponding, LALAPG mutation, Off-target, original, PET-CT |
| Date Added | 2023/11/23 - 12:44:35 |
| Date Modified | 2024/12/15 - 11:18:47 |
| Notes and Attachments | Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) Full Text (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) Texte intégral (Attachment) |
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