CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Therapeutic mRNAs for cancer immunotherapy: From structure to delivery.
Therapeutic mRNAs for cancer immunotherapy: From structure to delivery.
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mRNA携带遗传信息,在生物技术和医学领域用于合成蛋白质、蛋白片段及肽。mRNA导入细胞后,细胞机制会将其翻译为相应蛋白质。研究者设计了编码各种蛋白质、肽和蛋白片段的mRNA,以实现多种治疗目的,包括癌症治疗、免疫治疗、疫苗制备、组织工程和遗传病治疗等。此类疫苗可编码肿瘤特异性抗原,刺激免疫系统识别并攻击癌细胞。
此外,还可设计mRNA以产生调节免疫检查点的蛋白质,从而增强免疫系统靶向癌细胞的能力。合成mRNA还可用于改造T细胞等免疫细胞,提高其抗癌能力。例如,可通过工程化mRNA生成靶向癌细胞特定抗原的CAR-T 细胞。对于因特定蛋白缺失或缺陷而致病的遗传病患者,设计的mRNA可编码有功能的蛋白质。
然而,mRNA本身不稳定,可能需要特殊机制防止其降解。如何将mRNA递送至靶细胞仍是一项挑战。含mRNA的工程化纳米载体可提高递送效率并使其到达特定部位,提供治疗所需的刺激物或物质。这种组合可能提高其在多种治疗应用中的稳定性和效能。下文介绍基于mRNA的癌症治疗基础进展,并概述mRNA纳米治疗在关键临床前开发阶段及不断演变的临床领域中的进展。
mRNA carries genetic information and is used for the synthesis of proteins, fragments of proteins, and peptides in the scope of biotechnology and medicine. Once introduced into cells, this mRNA gets translated into a corresponding protein with cellular machinery.
All kinds of mRNA encoding any protein, peptide, and fragment of proteins have been designed to be used for various therapeutic goals, including cancerous diseases, immunotherapy, vaccine preparation, tissue engineering, and genetic disorders, among others. These vaccines encode tumor-specific antigens that stimulate the immune system to recognize and attack cancer cells.
Additionally, mRNA can be designed to produce proteins that modulate immune checkpoints, thereby enhancing the immune system's ability to target cancer cells. Synthetic mRNA can also engineer immune cells, such as T cells, to improve their cancer-fighting capabilities. For instance, mRNA can be engineered to generate CAR T cells targeting specific antigens that are expressed in the cancer. Designed mRNA can encode functional proteins in patients suffering from genetic disorders characterized by an absence or defect in a particular protein.
However, mRNA is intrinsically unstable and may require special mechanisms to protect it from degradation. mRNA delivery to target cells remains a challenge. Engineered nanocarriers containing mRNA can improve the efficiency and enable the delivery to specific sites, that can provide a stimulant or substance for therapeutic purposes.
This combination may improve their stability and efficacy in multiple applications of therapies. The following chapter throws light on basic advances in mRNA-based cancer therapy and provides insights into the nanotherapeutics using mRNA in key preclinical developments and the evolving clinical landscape.
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