An IL-12-Based Nanocytokine Safely Potentiates Anticancer Immunity through Spatiotemporal Control of Inflammation to Eradicate Advanced Cold Tumors.

Feb 06, 2023

Experts: Pengwen Chen,Wenqian Yang,Koji Nagaoka,George Lo Huang,Takuya Miyazaki,Taehun Hong,Shangwei Li,Kazunori Igarashi,Kazuyoshi Takeda,Kazuhiro Kakimi,Kazunori Kataoka,Horacio Cabral

Treatment of immunologically cold tumors is a major challenge for immune checkpoint inhibitors (ICIs). Interleukin 12 (IL-12) can invigorate ICIs against cold tumors by establishing a robust antitumor immunity. However, its toxicity and systemic induction of counteracting immunosuppressive signals have hindered translation. Here, IL-12 activity is spatiotemporally controlled for safely boosting efficacy without the stimulation of interfering immune responses by generating a nanocytokine that remains inactive at physiological pH, but unleashes its full activity at acidic tumor pH. The IL-12-based nanocytokine (Nano-IL-12) accumulate and release IL-12 in tumor tissues, eliciting localized antitumoral inflammation, while preventing systemic immune response, counteractive immune reactions, and adverse toxicities even after repeated intravenous administration. The Nano-IL-12-mediated spatiotemporal control of inflammation prompt superior anticancer efficacy, and synergize with ICIs to profoundly inflame the tumor microenvironment and completely eradicate ICI-resistant primary and metastatic tumors. The strategy could be a promising approach toward safer and more effective immunotherapies.
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

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ABOUT THE EXPERTS

Pengwen Chen,Wenqian Yang,Koji Nagaoka,George Lo Huang,Takuya Miyazaki,Taehun Hong,Shangwei Li,Kazunori Igarashi,Kazuyoshi Takeda,Kazuhiro Kakimi,Kazunori Kataoka,Horacio Cabral

Pengwen Chen

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Wenqian Yang

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Koji Nagaoka

Department of Immunotherapeutics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

George Lo Huang

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Takuya Miyazaki

Red Arrow Therapeutics, Inc., 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0003, Japan.

Kanagawa Institute of Industrial Science and Technology, 705-1Shimoimaizumi, Ebina City, Kanagawa, 243-0435, Japan.

Taehun Hong

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Shangwei Li

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Kazunori Igarashi

Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Kazuyoshi Takeda

Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Laboratory of Cell Biology, Research Support Center, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Kazuhiro Kakimi

Department of Immunotherapeutics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Kazunori Kataoka

Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.

Horacio Cabral

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.