First-in-human study of anticancer immunotherapy drug candidate mobilan: safety, pharmacokinetics and pharmacodynamics in prostate cancer patients.

// Natalia V. Eremina 1 , Vasily I. Kazey 1 , Sergey V. Mishugin 2 , Roman V. Leonenkov 3 , Dmitry Y. Pushkar 4 , Vadim L. Mett 5 and Andrei V. Gudkov 6 1 Panacela Labs LLC, Moscow, Russian Federation 2 D.D. Pletnev Municipal Clinical Hospital, Moscow Department of Healthcare, Moscow, Russian Federation 3 St. Petersburg Clinical Research and Practical Center for Specialized Oncological Medical Care, St. Petersburg, Russian Federation 4 S.I. Spasokukotsky Municipal Clinical Hospital, Moscow Department of Healthcare, Moscow, Russian Federation 5 Buffalo BioLabs LLC, Buffalo, NY, USA 6 Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA Correspondence to: Vasily I. Kazey, email: vkazey@panacelalabs.com Andrei V. Gudkov, email: andrei.gudkov@roswellpark.org Keywords: prostate cancer; immunotherapy; mobilan; adenoviral vector; intratumor injection Received: February 10, 2020     Accepted: March 14, 2020     Published: April 07, 2020 ABSTRACT Toll-like receptor 5 (TLR5) controls endogenous immune responses to pathogens and is a promising target for pharmacological stimulation of anti-tumor immunity. Mobilan is an innovative gene therapy agent consisting of a non-replicating bicistronic adenovirus directing constitutive expression of human Toll-like receptor 5 (TLR5) and the secreted flagellin-based TLR5 agonist, 502s. In mice, Mobilan injection into prostate tumors resulted in autocrine TLR5 signaling, immune system activation, and suppression of tumor growth and metastasis. Here we report a first-in-human placebo-controlled clinical study of Mobilan aimed at evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of a single intra-prostate injection of Mobilan in early stage prostate cancer patients. Mobilan was safe and well-tolerated at all tested doses; thus, the maximum tolerated dose was not identified. Injection of Mobilan induced signs of self-resolving inflammation not present in placebo-injected patients, including transient elevation of PSA and cytokine (G-CSF, IL-6) levels, and increased lymphoid infiltration in prostate tissue. The highest dose of Mobilan (10 11 viral particles) produced the best combination of safety and pharmacodynamic effects. Therefore, Mobilan is well-tolerated and induces the expected pharmacodynamic response in humans. These results support further clinical development of Mobilan as a novel immunotherapy for prostate cancer.