Miliotou Androulla N, Georgiou-Siafis Sofia K, Ntenti Charikleia, Pappas Ioannis S, Papadopoulou Lefkothea C
Laboratory of Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Macedonia, Greece.
Department of Health Sciences, KES College, 1055 Nicosia, Cyprus.
Curr Issues Mol Biol. 2023 Nov 16;45(11):9181-9214. doi: 10.3390/cimb45110576.
Over 100 innovative in vitro transcribed (IVT)-mRNAs are presently undergoing clinical trials, with a projected substantial impact on the pharmaceutical market in the near future. Τhe idea behind this is that after the successful cellular internalization of IVT-mRNAs, they are subsequently translated into proteins with therapeutic or prophylactic relevance. Simultaneously, cancer immunotherapy employs diverse strategies to mobilize the immune system in the battle against cancer. Therefore, in this review, the fundamental principles of IVT-mRNA to its recruitment in cancer immunotherapy, are discussed and analyzed. More specifically, this review paper focuses on the development of mRNA vaccines, the exploitation of neoantigens, as well as Chimeric Antigen Receptor (CAR) T-Cells, showcasing their clinical applications and the ongoing trials for the development of next-generation immunotherapeutics. Furthermore, this study investigates the synergistic potential of combining the CAR immunotherapy and the IVT-mRNAs by introducing our research group novel, patented delivery method that utilizes the Protein Transduction Domain (PTD) technology to transduce the IVT-mRNAs encoding the CAR of interest into the Natural Killer (NK)-92 cells, highlighting the potential for enhancing the CAR NK cell potency, efficiency, and bioenergetics. While IVT-mRNA technology brings exciting progress to cancer immunotherapy, several challenges and limitations must be acknowledged, such as safety, toxicity, and delivery issues. This comprehensive exploration of IVT-mRNA technology, in line with its applications in cancer therapeutics, offers valuable insights into the opportunities and challenges in the evolving landscape of cancer immunotherapy, setting the stage for future advancements in the field.
目前,超过100种创新的体外转录(IVT)-mRNA正在进行临床试验,预计在不久的将来会对制药市场产生重大影响。其背后的理念是,IVT-mRNA成功内化进入细胞后,随后会被翻译成具有治疗或预防意义的蛋白质。同时,癌症免疫疗法采用多种策略来调动免疫系统对抗癌症。因此,在本综述中,将讨论和分析IVT-mRNA在癌症免疫治疗中的基本原理及其应用。更具体地说,本综述文章重点关注mRNA疫苗的开发、新抗原的利用以及嵌合抗原受体(CAR)T细胞,展示它们的临床应用以及下一代免疫疗法开发的正在进行的试验。此外,本研究通过介绍我们研究小组新颖的、已获专利的递送方法来研究将CAR免疫疗法与IVT-mRNAs相结合的协同潜力,该方法利用蛋白质转导结构域(PTD)技术将编码感兴趣的CAR的IVT-mRNAs转导到自然杀伤(NK)-92细胞中,突出了增强CAR NK细胞效力、效率和生物能量学的潜力。虽然IVT-mRNA技术为癌症免疫治疗带来了令人兴奋的进展,但必须认识到一些挑战和局限性,如安全性、毒性和递送问题。对IVT-mRNA技术的全面探索及其在癌症治疗中的应用,为癌症免疫治疗不断发展的格局中的机遇和挑战提供了有价值的见解,为该领域的未来进展奠定了基础。
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