News Release

Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence

Peer-Reviewed Publication

Compuscript Ltd

https://doi.org/10.1016/j.apsb.2023.08.034

 

This new article publication from Acta Pharmaceutica Sinica B, discusses cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence.

 

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. The authors of this article describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy.

 

VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation.

 

The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

 

 

Keywords: Virus-like vesicles, Oncolytic virus, IL-12, IL-17, PD-L1, T cell exhaustion, Combination therapy, Cancer immunotherapy

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383523003416-ga1_lrg.jpg

CARG-2020 delivers a single chain IL-12, shRNA against PD-L1, and an antagonist of IL-17RA. These payloads stimulate Th1-armed immunity, reduce PD-L1 expression, and suppress cancer-promoting inflammation.

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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

For more information please visit https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/

Editorial Board: https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/editorial-board

 

APSB is available on ScienceDirect (https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b).

 

Submissions to APSB may be made using Editorial Manager® (https://www.editorialmanager.com/apsb/default.aspx).

 

CiteScore: 19.4

Impact Factor: 14.5

JIF without self-citation: 13.7

ISSN 2211-3835

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Ju Chen, Bhaskara Reddy Madina, Elham Ahmadi, Timur Olegovich Yarovinsky, Marie Marthe Krady, Eileen Victoria Meehan, Isabella China Wang, Xiaoyang Ye, Elise Pitmon, Xian-Yong Ma, Bijan Almassian, Valerian Nakaar, Kepeng Wang, Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence, Acta Pharmaceutica Sinica B, Volume 14, Issue 1, 2024, Pages 335-349, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2023.08.034


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