基于mRNA-LNP的肿瘤免疫疗法

mRNA-LNP-based cancer immunotherapy

新兴的肿瘤免疫疗法是通过激活抗原特异性T细胞来实现强大的抗肿瘤反应,尽管其取得了令人瞩目的进展,但许多肿瘤患者对这些抗肿瘤疗法仅部分出现反应或根本没有反应。mRNA-脂质纳米颗粒(mRNA-LNP)技术可以应用于肿瘤免疫治疗,目前正在多个领域进行研究,包括治疗性肿瘤疫苗、双特异性抗体、细胞因子、共刺激配体和受体以及CAR-T细胞治疗等,而其中研究比较集中的领域则是治疗性肿瘤疫苗和肿瘤内免疫治疗。治疗性肿瘤疫苗使用编码含有在肿瘤中发现的突变肽,即创建一种由患者肿瘤特有的由新抗原组成的个性化肿瘤疫苗。肿瘤内免疫治疗是通过提供编码有效免疫刺激蛋白的mRNA将免疫细胞浸润很少的“冷”肿瘤转化为免疫细胞浸润增加的“热”肿瘤,以在有限的全身毒性的情况下促进有效的抗肿瘤免疫活性。m RNA-LNP技术在肿瘤免疫疗法的多个领域的应用为肿瘤免疫治疗注入了新的活力。

Emerging cancer immunotherapies achieve robust antitumor responses by activating antigen-specific T cells.Despite the tremendous progresses,many cancer patients respond only partially or not at all to these anticancer therapies.m RNA-lipid nanoparticles(mRNA-LNP)technology can be applied to tumor immunotherapy and is currently being studied in various fields,including therapeutic tumor vaccines,bispecific antibodies,cytokines,costimulatory ligands and receptors and CAR-T cell therapy.The most concentrated research areas are therapeutic cancer vaccines and intratumoral immunotherapy.Therapeutic tumor vaccines use encoding peptides that contain mutations found in the patient’s tumor,creating a personalized tumor vaccine composed of neoantigens specific to the patient’s tumor.Intratumoral immunotherapy transforms"cold"tumors with little immune cell infiltration into"hot"tumors with increased immune cell infiltration by delivering mRNA encoding potent immune-stimulatory proteins to promote superior anti-tumor immune response with limited systemic toxicity.Tumor immunotherapy is reinvigorated after the application of m RNA-LNP technology in multiple fields of tumor immunotherapy.