First-in-human study of anticancer immunotherapy drug candidate mobilan: safety, pharmacokinetics and pharmacodynamics in prostate cancer patients
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Natalia V. Eremina1, Vasily I. Kazey1, Sergey V. Mishugin2, Roman V. Leonenkov3, Dmitry Y. Pushkar4, Vadim L. Mett5 and Andrei V. Gudkov6
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
|Vasily I. Kazey,||email:||[email protected]|
|Andrei V. Gudkov,||email:||[email protected]|
Keywords: prostate cancer; immunotherapy; mobilan; adenoviral vector; intratumor injection
Received: February 10, 2020 Accepted: March 14, 2020 Published: April 07, 2020
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 (1011 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.
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