通过LNP-RNA介导的抗原呈现利用了SARS-CoV-2特异性免疫力来治疗癌症
Yonger Xue1,2,3,4, Xucheng Hou5,6,7, Yichen Zhong2,3,4
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Nature communications
|March 4, 2025
概括
新的脂质纳米粒子 (LNP) 平台可以重定向现有的T细胞免疫力对抗SARS-CoV-2尖端蛋白,以向并抑制在临床前模型中的癌症生长. 这种方法对癌症治疗有希望.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米技术纳米技术
- 在瘤学瘤学.
背景情况:
- 脂质纳米粒子 (LNP) -mRNA针对SARS-CoV-2的疫苗已经产生了广泛的T细胞免疫力,准了尖端蛋白.
- 这种现有的尖端特异性T细胞免疫力为癌症免疫疗法提供了潜在的普遍目标.
研究的目的:
- 通过重定向尖端特异性T细胞免疫力来开发和评估用于癌症治疗的新型LNP-RNA平台.
- 评估工程LNP在输送RNA有效载荷的有效性,以对抗瘤的抗原呈现.
主要方法:
- 新型氨基醇或氨基酸衍生的电离性脂质 (AA脂质) 的合成,用于LNP配方.
- 开发LNP封装尖峰mRNA用于T细胞原始化和LNP输送自我放大RNA (saRNAs) 编码尖峰表位载MHC I分子 (sSE-SCTs) 进行抗原呈现.
- 在体内研究与B16F10黑色素瘤和A20淋巴瘤的小鼠模型,和ex vivo研究与人类癌症样本.
主要成果:
- 在提供尖端mRNA时,AA2 LNP与FDA批准的LNP相比,表现出优异的T细胞免疫诱导.
- AA15V LNP有效地将编码sSE-SCT的saRNA传递到瘤组织中,诱导尖端表位表现.
- 在接种疫苗的小鼠中,用AA15V LNP-sSE-SCTs进行内治疗抑制了瘤生长并延长了生存时间.
- AA15V LNP-sSE-SCTs 在人体质母细胞瘤和肺癌样本中的表达.
结论:
- 新型AA脂基LNP是癌症免疫治疗的有效输送工具.
- 使用LNP-RNA平台重定向先前存在的尖端特异性T细胞免疫力,可以抑制瘤生长.
- 开发的平台具有在癌症治疗中临床翻译的潜力.
相关概念视频
Tumor Immunotherapy
461
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
461
Cancer Vaccines
324
Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
324
Rous Sarcoma Virus (RSV) and Cancer
4.9K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
4.9K
Targeted Cancer Therapies
7.4K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.4K
Cytotoxic T Cells-mediated Immune Response
825
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
825


