Full text

Turn on search term navigation

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

The maintenance of the structural integrity of therapeutic proteins in the target tissue is crucial to their proper function. In this study, we aimed to assess the in vivo stability of the therapeutic protein Omomyc in blood serum and tumor tissue in a xenograft mouse model of colorectal cancer. As Omomyc represents a new clinical modality to target MYC, a most wanted target found deregulated in the majority of human cancers, our findings provide grounds to support the administration regimen in solid tumors. Moreover, we show that this method could apply to paraffin-embedded clinical biopsies for direct protein detection in patient samples.

Abstract

MYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.

Details

Title
Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue
Author
Beaulieu, Marie-Eve 1 ; Martínez-Martín, Sandra 1 ; Kaur, Jastrinjan 2 ; Virginia Castillo Cano 1 ; Massó-Vallés, Daniel 1 ; Laia Foradada Felip 1 ; López-Estévez, Sergio 1 ; Erika Serrano del Pozo 2 ; Thabussot, Hugo 1 ; Soucek, Laura 3   VIAFID ORCID Logo 

 Peptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain 
 Preclinical & Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain 
 Peptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; Preclinical & Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain 
First page
826
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2774885540
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.