Fc-engineered monoclonal antibodies to reduce off-target liver uptake
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-09-01
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| Series: | EJNMMI Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13550-023-01030-0 |
| _version_ | 1797556545156808704 |
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| author | Tristan Mangeat Matthieu Gracia Alexandre Pichard Sophie Poty Pierre Martineau Bruno Robert Emmanuel Deshayes |
| author_facet | Tristan Mangeat Matthieu Gracia Alexandre Pichard Sophie Poty Pierre Martineau Bruno Robert Emmanuel Deshayes |
| author_sort | Tristan Mangeat |
| collection | DOAJ |
| description | 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; FcγR). 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 FcγR display lower liver accumulation and better tumor-to-liver ratios. These findings need to be taken into account to improve antibody-based theragnostic approaches. |
| first_indexed | 2024-03-10T17:03:25Z |
| format | Article |
| id | doaj.art-ef2f33b9aff744cb8b78af90bd6122a6 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-03-10T17:03:25Z |
| publishDate | 2023-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-ef2f33b9aff744cb8b78af90bd6122a62023-11-20T10:53:36ZengSpringerOpenEJNMMI Research2191-219X2023-09-011311610.1186/s13550-023-01030-0Fc-engineered monoclonal antibodies to reduce off-target liver uptakeTristan Mangeat0Matthieu Gracia1Alexandre Pichard2Sophie Poty3Pierre Martineau4Bruno Robert5Emmanuel Deshayes6Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université de Montpellier, ICMAbstract 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; FcγR). 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 FcγR display lower liver accumulation and better tumor-to-liver ratios. These findings need to be taken into account to improve antibody-based theragnostic approaches.https://doi.org/10.1186/s13550-023-01030-0PET-CTFc gamma receptorOff-targetFcLALAPG mutation |
| spellingShingle | Tristan Mangeat Matthieu Gracia Alexandre Pichard Sophie Poty Pierre Martineau Bruno Robert Emmanuel Deshayes Fc-engineered monoclonal antibodies to reduce off-target liver uptake EJNMMI Research PET-CT Fc gamma receptor Off-target Fc LALAPG mutation |
| title | Fc-engineered monoclonal antibodies to reduce off-target liver uptake |
| title_full | Fc-engineered monoclonal antibodies to reduce off-target liver uptake |
| title_fullStr | Fc-engineered monoclonal antibodies to reduce off-target liver uptake |
| title_full_unstemmed | Fc-engineered monoclonal antibodies to reduce off-target liver uptake |
| title_short | Fc-engineered monoclonal antibodies to reduce off-target liver uptake |
| title_sort | fc engineered monoclonal antibodies to reduce off target liver uptake |
| topic | PET-CT Fc gamma receptor Off-target Fc LALAPG mutation |
| url | https://doi.org/10.1186/s13550-023-01030-0 |
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