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
Author(s)
D'Onofrio A., Gano L., Melo R., Mendes F., Cristina Oliveira M., Denoël T., Schaefer N., Viertl D., Fierle J., Coukos G., Dunn S., Prior J.O., Paulo A.
ISSN
1873-3441 (Electronic)
ISSN-L
0939-6411
Publication state
Published
Issued date
30/11/2020
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
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
Antibody fragments, Radioimmunotherapy, Radioiodine, TEM1, Theranostics
Pubmed
Create date
10/12/2020 15:56
Last modification date
11/12/2020 6:27
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