Advancements of engineered live oncolytic biotherapeutics (microbe/virus/cells): Preclinical research and clinical progress,Journal of Controlled Release

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Advancements of engineered live oncolytic biotherapeutics (microbe/virus/cells): Preclinical research and clinical progress
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-09-11 , DOI: 10.1016/j.jconrel.2024.09.006
Zhengzhuo Qi ₁ , Junmou Gu ₂ , Lihang Qu ₃ , Xianbao Shi ₄ , Zhonggui He ₅ , Jin Sun ₅ , Lingchen Tan ₆ , Mengchi Sun ₇

Affiliation

The proven efficacy of immunotherapy in fighting tumors has been firmly established, heralding a new era in harnessing both the innate and adaptive immune systems for cancer treatment. Despite its promise, challenges such as inefficient delivery, insufficient tumor penetration, and considerable potential toxicity of immunomodulatory agents have impeded the advancement of immunotherapies. Recent endeavors in the realm of tumor prophylaxis and management have highlighted the use of living biological entities, including bacteria, oncolytic viruses, and immune cells, as a vanguard for an innovative class of live biotherapeutic products (LBPs). These LBPs are gaining recognition for their inherent ability to target tumors. However, these LBPs must contend with significant barriers, including robust immune clearance mechanisms, cytotoxicity and other in vivo adverse effects. Priority must be placed on enhancing their safety and therapeutic indices. This review consolidates the latest preclinical research and clinical progress pertaining to the exploitation of engineered biologics, spanning bacteria, oncolytic viruses, immune cells, and summarizes their integration with combination therapies aimed at circumventing current clinical impasses. Additionally, the prospective utilities and inherent challenges of the biotherapeutics are deliberated, with the objective of accelerating their clinical application in the foreseeable future.

中文翻译：

工程活溶瘤生物治疗药物（微生物/病毒/细胞）的进展：临床前研究和临床进展

免疫疗法在对抗肿瘤方面的行之有效的疗效已经得到证实，预示着利用先天免疫系统和适应性免疫系统进行癌症治疗的新时代。尽管免疫调节剂前景广阔，但递送效率低下、肿瘤渗透不足和免疫调节剂的巨大潜在毒性等挑战阻碍了免疫疗法的发展。肿瘤预防和管理领域的最新努力突出了活生物实体（包括细菌、溶瘤病毒和免疫细胞）的使用，作为一类创新活体生物治疗产品（LBP）的先锋。这些 LBP 因其靶向肿瘤的固有能力而获得认可。然而，这些 LBP 必须与重大障碍作斗争，包括强大的免疫清除机制、细胞毒性和其他体内不良反应。必须优先考虑提高其安全性和治疗指数。本综述整合了与工程生物制剂开发有关的最新临床前研究和临床进展，涵盖细菌、溶瘤病毒、免疫细胞，并总结了它们与旨在规避当前临床僵局的联合疗法的整合。此外，还考虑了生物治疗药物的潜在效用和固有挑战，目的是在可预见的未来加速其临床应用。

更新日期：2024-09-11

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