دورية أكاديمية
Biological evaluation of new TEM1 targeting recombinant antibodies for radioimmunotherapy: In vitro, in vivo and in silico studies.
| العنوان: | Biological evaluation of new TEM1 targeting recombinant antibodies for radioimmunotherapy: In vitro, in vivo and in silico studies. |
|---|---|
| المؤلفون: | D'Onofrio, A., Gano, L., Melo, R., Mendes, F., Oliveira, M.C., Denoël, T., Schaefer, N., Viertl, D., Fierle, J., Coukos, G., Dunn, S., Prior, J.O., Paulo, A. |
| المصدر: | European journal of pharmaceutics and biopharmaceutics, vol. 158, pp. 233-244 |
| سنة النشر: | 2021 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Animals, Antigens, CD/metabolism, Neoplasm/metabolism, Cell Line, Tumor, Complementarity Determining Regions/genetics, Computer Simulation, Female, Humans, Immunoconjugates/administration & dosage, Immunoconjugates/genetics, Immunoconjugates/pharmacokinetics, Iodine Radioisotopes, Mice, Mutation, Neoplasms/radiotherapy, Radioimmunotherapy/methods, Recombinant Proteins/administration & dosage, Recombinant Proteins/genetics, Recombinant Proteins/pharmacokinetics, Single-Chain Antibodies/administration & dosage, Single-Chain Antibodies/genetics, Single-Chain Antibodies/pharmacokinetics, Tissue Distribution, Xenograft Model Antitumor Assays, Antibody fragments, Radioimmunotherapy, Radioiodine, TEM1 |
| الوصف: | The tumour endothelial marker 1 (TEM1/endosialin/CD248) is a receptor overexpressed in several human solid tumours and silenced in normal adult tissues, representing a suitable and potentially safe target for radioimmunotherapy of sarcoma. To develop new tools with improved TEM1 targeting properties, a new panel of antibody fragments was for the first time evaluated preclinically following 125 I radiolabelling. The antibody fragment 1C1m-Fc, with the highest human/murine TEM1 binding affinity, was extensively characterized in vitro and in vivo in a Ewing's sarcoma human xenograft mouse model. In silico studies were also performed to elucidate the influence of a single amino acid mutation in the complementarity-determining region (CDR3) of the heavy chain, upon affinity maturation of the parental clone 1C1-Fc. From this study, 1C1m-Fc emerged as a promising candidate for the development of TEM1-targeted radioimmunoconjugates, namely to be further explored for theranostic applications with other suitable medical radionuclides. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0939-6411 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33271301; info:eu-repo/semantics/altIdentifier/eissn/1873-3441; https://serval.unil.ch/notice/serval:BIB_95FD98ADDB6DTest; urn:issn:0939-6411 |
| DOI: | 10.1016/j.ejpb.2020.11.015 |
| الإتاحة: | https://doi.org/10.1016/j.ejpb.2020.11.015Test https://serval.unil.ch/notice/serval:BIB_95FD98ADDB6DTest |
| رقم الانضمام: | edsbas.B65A180E |
| قاعدة البيانات: | BASE |
| تدمد: | 09396411 |
|---|---|
| DOI: | 10.1016/j.ejpb.2020.11.015 |