Safety and efficacy of p62 DNA vaccine ELENAGEN in a first-in-human trial in patients with advanced solid tumors

// Dmitry M. Ponomarenko 1 , Irina D. Klimova 1 , Yulia A. Chapygina 1 , Viktoria V. Dvornichenko 1 , Natalia V. Zhukova 2 , Rashida V. Orlova 2,3 , Georgy M. Manikhas 2,4 , Alexandr V. Zyryanov 5 , Lilya A. Burkhanova 5 , Irina I. Badrtdinova 5 , Basile N. Oshchepkov 5 , Elena V. Filippova 4 , Sergei V. Orlov 4 , Sergei I. Kolesnikov 6 , Albert A. Sufianov 7,8 , Svetlana R. Baum 9 , Olga Y. Zaitzeva 9 , Andrey B. Komissarov 10 , Mikhail P. Grudinin 10 , Oleg I. Kiselev 10,* , Anatoly F. Tsyb 11,* , Franco Venanzi 12 , Vita Shcherbinina 13 , Andrey Chursov 13,14 ,Vladimir L. Gabai 13,14,15 and Alexander M. Shneider 8,14,16 1 Irkutsk State Medical Academy of Postgraduate Education, Irkutsk Regional Cancer Dispensary, Irkutsk, Russian Federation 2 Saint-Petersburg City Clinical Oncology Dispensary, Saint-Petersburg, Russian Federation 3 Saint-Petersburg University, Saint-Petersburg, Russian Federation 4 Pavlov First Saint Petersburg State Medical University, Saint- Petersburg, Russian Federation 5 Multidisciplinary Clinical Medical Center "Medical City", Tyumen, Russian Federation 6 Russian Academy of Sciences, Moscow, Russian Federation 7 Federal Center of Neurosurgery, Tyumen, Russian Federation 8 Sechenov First Moscow State Medical University, Moscow, Russian Federation 9 Synergy Research Group, Moscow, Russian Federation 10 Research Institute of Influenza, Saint-Petersburg, Russian Federation 11 A. Tsyb Medical Radiological Research Center, Obninsk, Russian Federation 12 Department of Biology MCA, University of Camerino, Italy 13 CL Oncology, LLC, Moscow, Russian Federation 14 CureLab Oncology, Inc, Dedham, MA, USA 15 Department of Biochem, Boston University School of Medicine, Boston, MA, USA 16 Department of Molecular Biology, Ariel University, Ariel, Israel * deceased Correspondence to: Vladimir L. Gabai, email: // Alexander M. Shneider , email: // Keywords : cancer immunotherapy; chemotherapy; cancer vaccine; breast cancer; ovary cancer Received : February 14, 2017 Accepted : March 16, 2017 Published : March 25, 2017 Abstract Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose. Ten patients with breast and ovary cancers that progressed after Elenagen were then treated with conventional chemotherapy. Adverse events (AE) were of Grade 1; no severe AE were observed. Cumulatively twelve patients (44%) with breast, ovary, lung, renal cancer and melanoma achieved stable disease for at least 8 wks, with 4 of them (15%) had tumor control for more than 24 wks, with a maximum of 32 wks. The patients with breast and ovary cancers achieved additional tumor stabilization for 12-28 wks when treated with chemotherapy following Elenagen treatment. Therefore, Elenagen demonstrated good safety profile and antitumor activity in advanced solid tumors. Especially encouraging is its ability to restore tumor sensitivity to chemotherapy.