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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1455019
This article is part of the Research Topic Nanoparticles for Cancer Immunotherapy: from Basics to Clinics View all 9 articles

Local administration of mRNA encoding cytokine cocktail confers potent anti-tumor immunity

Provisionally accepted
ZHIGANG LI ZHIGANG LI Yucai Peng Yucai Peng *LING HU LING HU YI WANG YI WANG QI LIU QI LIU JUN LIU JUN LIU HAIYAN LONG HAIYAN LONG QI LI QI LI LIPING LUO LIPING LUO
  • Liverna Therapeutics Inc., Zhuhai, China

The final, formatted version of the article will be published soon.

    Immunotherapy using inflammatory cytokines, such as interleukin (IL)-2 and interferon (IFN)-α, has been clinically validated in treating various cancers. However, systemic immunocytokine-based therapies are limited by the short half-life of recombinant proteins and severe dose-limiting toxicities.In this study, we exploited local immunotherapy by intratumoral administration of lipid nanoparticle (LNP)-encapsulated mRNA cocktail encoding cytokines IL-12, IL-7, and IFN-α. The cytokine mRNA cocktail induced tumor regression in multiple syngeneic mouse models and anti-tumor immune memory in one syngeneic mouse model. Additionally, immune checkpoint blockade further enhanced the anti-tumor efficacy of the cytokine mRNAs. Furthermore, human cytokine mRNAs exhibited robust anti-tumor efficacy in humanized mouse tumor models. Mechanistically, cytokine mRNAs induced tumor microenvironment inflammation, characterized by robust T cell infiltration and significant inflammatory cytokine and chemokine production.

    Keywords: cytokine, mRNA, cancer immunotherapy, Intratumoral administration, Interleukin-12

    Received: 26 Jun 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 LI, Peng, HU, WANG, LIU, LIU, LONG, LI and LUO. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yucai Peng, Liverna Therapeutics Inc., Zhuhai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.