Biological evaluation of new TEM1 targeting recombinant antibodies for radioimmunotherapy: In vitro, in vivo and in silico studies.
Details
Serval ID
serval:BIB_95FD98ADDB6D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Biological evaluation of new TEM1 targeting recombinant antibodies for radioimmunotherapy: In vitro, in vivo and in silico studies.
Journal
European journal of pharmaceutics and biopharmaceutics
ISSN
1873-3441 (Electronic)
ISSN-L
0939-6411
Publication state
Published
Issued date
01/2021
Peer-reviewed
Oui
Volume
158
Pages
233-244
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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 <sup>125</sup> 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.
Keywords
Animals, Antigens, CD/metabolism, Antigens, 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, Theranostics
Pubmed
Create date
10/12/2020 15:56
Last modification date
28/09/2021 5:57