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Investigational New Drugs

Erschienen in:

28.04.2021 | PRECLINICAL STUDIES

Concomitant inhibition of B7-H3 and PD-L1 expression by a novel and synthetic microRNA delivers potent antitumor activities in colorectal tumor models

verfasst von: Fanyi Meng, Yinshuang Chen, Man Yang, Hongjian Zhang, Weipeng Wang

Erschienen in: Investigational New Drugs | Ausgabe 5/2021

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Summary

The families of miR-34 and miR-449 share the same seed region. However, the members showed differential effects on the expression of B7-H3 and PD-L1 in HCT-116 cells. Using miR-34a as a template, the non-seed region was modified by nucleotide alteration, yielding four synthetic microRNA (miRNA) analogs. Among those, NS-MX3, with a base alteration from G to C at the 18th locus of miR-34a, showed the most potent inhibition on both B7-H3 and PD-L1 expression. Subsequent investigations demonstrated that NS-MX3 had a broad anti-proliferation activity against several colorectal tumor cell lines and its antitumor effect was consistently reflected by tumor growth inhibition (TGI) in the HCT-116 xenograft model. In addition, NS-MX3 displayed a synergistic effect on TGI when combined with bevacizumab or regorafenib. Further analysis revealed that the superior antitumor activity of NS-MX3 was correlated to concomitant suppression of both B7-H3 and PD-L1 expression in tumor tissues. Taken together, the present study indicates that the non-seed region of miRNAs plays an important role in the regulation of checkpoint genes, thus showcasing single nucleotide alteration of the non-seed region as a promising approach to discover and develop novel immunotherapies.

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Titel: Concomitant inhibition of B7-H3 and PD-L1 expression by a novel and synthetic microRNA delivers potent antitumor activities in colorectal tumor models
verfasst von: Fanyi Meng
Yinshuang Chen
Man Yang
Hongjian Zhang
Weipeng Wang
Publikationsdatum: 28.04.2021
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 5/2021
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-021-01123-4

Springer Medizin

Concomitant inhibition of B7-H3 and PD-L1 expression by a novel and synthetic microRNA delivers potent antitumor activities in colorectal tumor models

Summary

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Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Summary

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