Beaulieu Marie-Eve, Martínez-Martín Sandra, Kaur Jastrinjan, Castillo Cano Virginia, Massó-Vallés Daniel, Foradada Felip Laia, López-Estévez Sergio, Serrano Del Pozo Erika, Thabussot Hugo, Soucek Laura
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.
Cancers (Basel). 2023 Jan 29;15(3):826. doi: 10.3390/cancers15030826.
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.
MYC是一种致癌蛋白，与大多数人类癌症有因果关系，也是癌症治疗中最受关注的靶点。Omomyc是迄今为止特征最明确的MYC显性负性蛋白。在过去几年中，它已被开发成为一种用于实体瘤治疗的治疗性微型蛋白，最近已进入临床阶段。然而，由于治疗性蛋白质在体内的稳定性，尤其是在肿瘤附近的稳定性，可能会受到蛋白水解降解的影响，因此Omomyc作为一种有效的治疗剂的观念经常受到质疑。在本研究中，我们使用质谱方法评估了静脉注射后Omomyc在小鼠异种移植瘤活检组织中的稳定性。我们的数据有力地支持，Omomyc功能域（DNA结合和二聚化区域）的完整性在给药后至少72小时内在肿瘤组织中保持完好，并且与血清相比，该蛋白在肿瘤区室中显示出优异的药代动力学。
