image: Figure 7: Proposed mode of action of INT-1B3/1B3.
INT-1B3/1B3 induces apoptosis and cell death leading to expression of DAMPs, e.g., expression of calreticulin, reduced expression of CD39 and CD73 and thus reduced levels of ATP. Release of DAMPs induces maturation of DC and these DC can activate CD4+, CD8+ and CD4-CD8- T cells upon stimulation. Activated CD4+, CD8+ and CD4-CD8- T cells produce IFNγ, TNFα and granzyme B which leads to cytotoxicity against tumor cells. This illustration was created with https://www.biorender.com/.
Credit: 2024 Duurland et al.
BUFFALO, NY- August 5, 2024 – A new research paper was published in Oncotarget's Volume 15 on July 12, 2024, entitled, “INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death.”
In this study, researchers Chantal L. Duurland, Thijs de Gunst, Harm C. den Boer, Marion T.J. van den Bosch, Bryony J. Telford, Rogier M. Vos, Xiaolei Xie, Mingfa Zang, Fang Wang, Yingying Shao, Xiaoyu An, Jingjing Wang, Jie Cai, Ludovic Bourré, Laurens A.H. van Pinxteren, Roel Q.J. Schaapveld, Michel Janicot, and Sanaz Yahyanejad from InteRNA Technologies BV, Utrecht, The Netherlands, and Crown Bioscience Inc., in San Diego, examined the effect of their lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity.
“In this study, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on animal survival, tumor microenvironment (TME) and induction of anti-tumor immune responses.”
The data presented within the study demonstrates for the first time that miR-193a-3p induces long-term immunity against tumor development via modulation of the tumor microenvironment and induction of immunogenic cell death.
Additionally, the data show that systemic administration of INT-1B3 to 4T1 and H22 tumor bearing immunocompetent mice prolonged animal survival by reducing metastasis compared to phosphate buffered saline (PBS) or anti-programmed death (PD) 1 treatment.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28608
Correspondence to: Sanaz Yahyanejad
Email: sanaz.yah@gmail.com
Keywords: miR-193a-3p, microRNA mimic, T cell mediated immunity, immunogenic cell death, cancer
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About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Animals
Article Title
INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death
Article Publication Date
12-Jul-2024
COI Statement
CLD, TG, HCB, MTJB, BJT, RMV, LAHP, RQJS, MJ, SY were employees of InteRNA Technologies BV and had stock options in the company when this study was performed. LAHP, RQJS and MJ were minority shareholders (<5%) in InteRNA Technologies BV. TG, RQJS, LAHP, MJ and SY are inventors of WO2019/155094 (2019). XX, MZ, FW, YS, XA, JW, JC, LB were employees of Crown Bioscience Inc., at the time of this study. The authors declare that this study was funded by InteRNA Technologies BV. The funder had the following involvement in the study: study design, data collection and analysis, interpretation of the results, decision to publish, and preparation of the manuscript.