Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue
Marie-Eve Beaulieu1, Sandra Martínez-Martín1, Jastrinjan Kaur2
1Peptomyc S.L., Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
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.
Insights
Omomyc, a MYC inhibitor, remains stable in tumors for over 72 hours post-administration. This cancer therapy shows better tumor pharmacokinetics than blood serum, supporting its clinical potential.
Area of Science:
- Oncology
- Molecular Biology
- Protein Therapeutics
Background:
- MYC is a crucial oncoprotein in numerous human cancers, making it a significant therapeutic target.
- Omomyc, a dominant-negative MYC inhibitor, has advanced to clinical trials for solid tumor treatment.
- Concerns exist regarding the in vivo stability of therapeutic proteins like Omomyc due to proteolytic degradation in tumors.
Purpose of the Study:
- To assess the stability and pharmacokinetics of Omomyc within tumor tissues after intravenous administration.
- To investigate the integrity of Omomyc's functional domains in the tumor microenvironment.
Main Methods:
- Utilized a mass spectrometry approach to analyze Omomyc stability.
- Evaluated Omomyc in tumor biopsies from murine xenograft models.
- Compared Omomyc pharmacokinetics in tumor tissue versus blood serum.
Main Results:
- Omomyc's functional domains (DNA binding and dimerization regions) remained intact in tumor tissue for at least 72 hours.
- Omomyc demonstrated superior pharmacokinetic properties within the tumor compartment compared to blood serum.
- Data support the preservation of Omomyc's integrity in vivo.
Conclusions:
- Omomyc exhibits significant stability within tumor tissues, addressing previous concerns about proteolytic degradation.
- The favorable pharmacokinetics of Omomyc in tumors support its viability as a therapeutic agent for cancer treatment.
- These findings bolster the clinical development of Omomyc for solid tumors.
