Author/Authors :
Sokolova, E.A Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia , Proshkina, G.M Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia , Kutova, O.M Lobachevsky State University of Nizhny Novgorod, Russia , Balalaeva, I.V Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia , Deyev, S.M Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences, Russia
Abstract :
The development of targeted toxins based on non-immunoglobulin targeting molecules appears to be one of the most advanced approaches in the targeted therapy of malignant tumors with a high expression of the HER2 receptor. Earlier, we showed that the targeted toxin DARPin-PE40 consisting of the HER2-specific non-immunoglobulin polypeptide (the targeting module) and a fragment of Pseudomonas exotoxin A (the toxic module) exhibits an antitumor effect in vivo againsttheHER2-positive adenocarcinoma xenograft. In this work, an in-depth analysis of the effect of DARPin-PE40 on the growth dynamics of experimental xenograft tumors was carried out. DARPin-PE40 was shown to inhibit tumor growth at a dose of 25 and 50 μg/animal and to cause tumor node reduction at a dose of 80 μg/animal, followed by growth resumption at the end of therapy. An evalu-ation of the tumor growth dynamics revealed statistically significant differences in tumor volume in mice in the experimental groups compared to the control group. The results testify to the potential of using the created targeted toxin as an agent for the targeted therapy of HER2-overexpressing tumors.
Keywords :
non-immunoglobulin module DARPin , tar-geted therapy , HER2 receptor , Pseudomonas aeruginosa exotoxin A
