دورية أكاديمية
Anticalin N- or C-Terminal on a Monoclonal Antibody Affects Both Production and In Vitro Functionality
| العنوان: | Anticalin N- or C-Terminal on a Monoclonal Antibody Affects Both Production and In Vitro Functionality |
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| المؤلفون: | Aubrey, Nicolas, Gouilleux-Gruart, Valérie, Dhommée, Christine, Mariot, Julie, Boursin, Fanny, Albrecht, Nicolas, Bergua, Cécile, Croix, Cecile, Gilotin, Mäelle, Haudebourg, Eloi, Horiot, Catherine, Matthias, Laetitia, Mouline, Caroline C, Lajoie, Laurie, Munos, Audrey, Ferry, Gilles, Viaud-Massuard, Marie-Claude, Thibault, Gilles, Velge-Roussel, Florence |
| المساهمون: | Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), GICC EA 7501, FRAME (Fc récepteur, anticorps et micro-environnement) (FRAME), Groupe innovation et ciblage cellulaire (GICC), EA 7501 2018-. (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), GICC EA 7501, IMT (Innovation moléculaire et thérapeutique) (IMT), Institut de Recherches SERVIER (IRS), Région Centre Val de Loire under the program “ARD2020 Biomédicaments—BIO-S”, ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010) |
| المصدر: | ISSN: 2073-4468 ; Antibodies ; https://hal.inrae.fr/hal-03771320Test ; Antibodies, 2022, 11 (3), 18 p. ⟨10.3390/antib11030054⟩ ; https://www.mdpi.com/2073-4468/11/3/54Test. |
| بيانات النشر: | HAL CCSD MDPI |
| سنة النشر: | 2022 |
| المجموعة: | Université François-Rabelais de Tours: HAL |
| مصطلحات موضوعية: | ADCC, CD16, CD32, CDC, Fc gamma receptors, FcRn, anticalin, bispecific antibody, monoclonal antibody, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IMM]Life Sciences [q-bio]/Immunology |
| الوصف: | International audience ; Bispecific antibodies (BsAbs) represent an important advance in innovative therapeutic strategies. Among the countless formats of BsAbs, fusion with molecules such as anticalins linked to a monoclonal antibody (mAb), represents an easy and low-cost way to obtain innovative molecules. We fused an anticalin against human fibronectin to a molecule biosimilar to trastuzumab (H0) or rituximab (R0), in four different positions, two on the N terminal region of heavy or light chains and two on the C terminal region. The eight BsAbs (H family (HF) 1 to 4 and R family (RF) 1 to 4) were produced and their affinity parameters and functional properties evaluated. The presence of anticalin did not change the glycosylation of the BsAb, shape or yield. The antigenic recognition of each BsAb family, Her2 for HF1 to 4 and CD20 for RF1 to 4, was slightly decreased (HF) or absent (RF) for the anticalin N-terminal in the light chain position. The anticalin recognition of FN was slightly decreased for the HF family, but a dramatic decrease was observed for RF members with lowest affinity for RF1. Moreover, functional properties of Abs, such as CD16 activation of NK, CD32-dependent phagocytosis and FcRn transcytosis, confirmed that this anticalin position leads to less efficient BsAbs, more so for RF than HF molecules. Nevertheless, all BsAbs demonstrated affinities for CD16, CD32 and FcRn, which suggests that more than affinity for FcRs is needed for a functioning antibody. Our strategy using anticalin and Abs allows for rapid generation of BsAbs, but as suggested by our results, some positions of anticalins on Abs result in less functionality. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35997348; hal-03771320; https://hal.inrae.fr/hal-03771320Test; https://hal.inrae.fr/hal-03771320/documentTest; https://hal.inrae.fr/hal-03771320/file/2022_Aubrey_antibodies_vol-11_art-54.pdfTest; PUBMED: 35997348; WOS: 000858081400001 |
| DOI: | 10.3390/antib11030054 |
| الإتاحة: | https://doi.org/10.3390/antib11030054Test https://hal.inrae.fr/hal-03771320Test https://hal.inrae.fr/hal-03771320/documentTest https://hal.inrae.fr/hal-03771320/file/2022_Aubrey_antibodies_vol-11_art-54.pdfTest |
| حقوق: | http://creativecommons.org/licenses/byTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.50031044 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/antib11030054 |
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