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局部纳米介导的白细胞介素-12基因疗法:癌症免疫治疗的有前景候选方案。

Localized Nano-mediated Interleukin-12 Gene Therapy: Promising Candidate for Cancer Immunotherapeutics.

作者信息

Venkatas Jeaneen, Singh Moganavelli

机构信息

Department of Biochemistry, Nano-Gene and Drug Delivery Laboratory, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.

出版信息

Curr Cancer Drug Targets. 2022;22(10):825-842. doi: 10.2174/1568009622666220609115109.

Abstract

BACKGROUND

Interleukin-12 (IL-12) has a pleiotropic nature that allows it to induce immune responses while reversing tumour-induced immunosuppression. Therefore, this paper discusses the application and potential of IL-12 as an antitumor immunotherapeutic agent, emphasizing its advantages and limitations and the need for and the development of localized IL-12 nano-delivery strategies in cancer immunotherapy.

METHODS

Several databases from the National Centre for Biotechnology Information, WorldCat.org and the National Library of Medicine were searched for peer-reviewed studies to assess the potential of localized nano-mediated interleukin-12 gene therapy for cancer treatment.

RESULTS

The literature search showed that IL-12 is a promising cancer immunotherapeutic agent. However, the systemic delivery of IL-12 was compromised by severe dose-limiting side effects, prompting the need for localized gene therapy to express the interleukin within the tumour microenvironment while minimizing systematic exposure. Although viral and non-viral gene therapy have demonstrated some efficacy in preclinical trials, the era of nanomedicine has opened novel avenues to improve therapeutic indices with minimal side effects. IL-12 activity can be further potentiated with other anticancer molecules that display immunostimulatory, autoantigenic and cytotoxic properties. Combination therapy has gained significant interest in the last decade as it increases gene therapy's therapeutic properties by decreasing the threshold for IL-12 efficacy and preventing systematic toxicity.

CONCLUSION

The findings of this article will provide researchers with the knowledge to create immunotherapeutic nanovectors which work synergistically with their therapeutic payload to enhance the therapeutic effect of the IL-12 gene to eliminate cancer cells.

摘要

背景

白细胞介素-12(IL-12)具有多效性,既能诱导免疫反应,又能逆转肿瘤诱导的免疫抑制。因此,本文讨论了IL-12作为抗肿瘤免疫治疗剂的应用和潜力,强调了其优势和局限性,以及在癌症免疫治疗中局部IL-12纳米递送策略的必要性和发展情况。

方法

检索了美国国立生物技术信息中心、WorldCat.org和美国国立医学图书馆的多个数据库,以查找同行评审研究,评估局部纳米介导的白细胞介素-12基因疗法在癌症治疗中的潜力。

结果

文献检索表明,IL-12是一种有前景的癌症免疫治疗剂。然而,IL-12的全身递送受到严重的剂量限制性副作用的影响,这促使需要进行局部基因治疗,以便在肿瘤微环境中表达白细胞介素,同时尽量减少全身暴露。尽管病毒和非病毒基因疗法在临床试验前已显示出一定疗效,但纳米医学时代为以最小副作用提高治疗指数开辟了新途径。IL-12的活性可通过其他具有免疫刺激、自身抗原和细胞毒性特性的抗癌分子进一步增强。在过去十年中,联合疗法引起了广泛关注,因为它通过降低IL-12疗效的阈值和预防全身毒性来提高基因治疗的治疗特性。

结论

本文的研究结果将为研究人员提供知识,以创建与治疗载荷协同作用的免疫治疗纳米载体,增强IL-12基因的治疗效果,从而消除癌细胞。

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