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活生物疗法GEN3013通过调节癌症进展和免疫系统增强癌症治疗的抗肿瘤疗效。

Live Biotherapeutic GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System.

作者信息

Kim Sujeong, Kim Yunjae, Lee Suro, Kim Yulha, Jeon Byungkwan, Kim Hyerim, Park Hansoo

机构信息

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.

Genome and Company, Pangyo-ro 255, Bundang-gu, Seoungnam 13486, Korea.

出版信息

Cancers (Basel). 2022 Aug 23;14(17):4083. doi: 10.3390/cancers14174083.

Abstract

The gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor immunity; however, others do not have such an effect or even promote tumor growth. Identifying effective strains that possess antitumor effects is key for developing live biotherapeutic anticancer products. Here, we found that GEN3013 inhibits tumor growth by regulating tumor angiogenesis and directly inducing cancer cell death. Moreover, GEN3013 enhanced the therapeutic effects of oxaliplatin and the PD-1 blockade. Comprehensive immune profiling showed that GEN3013 augmented cytotoxic immune cell populations, such as CD4 T cells, CD8 effector T cells, and NK cells in the tumor microenvironment. Our results indicate that GEN3013 is a promising candidate for potentiating cancer treatment in combination with current standard therapy.

摘要

肠道微生物群通过调节宿主免疫系统和肿瘤微环境,导致抗癌药物疗效存在差异。有趣的是,这种差异效应具有高度的菌株特异性。例如,某些菌株可直接抑制肿瘤生长并增强抗肿瘤免疫力;然而,其他菌株则没有这种作用,甚至会促进肿瘤生长。识别具有抗肿瘤作用的有效菌株是开发活体生物治疗抗癌产品的关键。在此,我们发现GEN3013通过调节肿瘤血管生成和直接诱导癌细胞死亡来抑制肿瘤生长。此外,GEN3013增强了奥沙利铂和PD-1阻断的治疗效果。全面的免疫分析表明,GEN3013增加了肿瘤微环境中细胞毒性免疫细胞群体,如CD4 T细胞、CD8效应T细胞和NK细胞。我们的结果表明,GEN3013是与当前标准疗法联合增强癌症治疗效果的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553f/9455052/a1687d7604fb/cancers-14-04083-g001.jpg

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