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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prospect of chimeric antigen receptor T-cell therapy for cancer.
Prospect of chimeric antigen receptor T-cell therapy for cancer.
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过继性细胞转移(ACT)是癌症免疫治疗中一种快速且有前景的新进展,其中CAR-T 细胞疗法旨在通过编程免疫系统来攻击肿瘤。工程化CAR受体随着嵌合抗原受体四代组成的不同而不断发展。第一代CAR-T 细胞不能产生足够的白细胞介素-2(IL-2)来消灭癌细胞。下一代增加了次级单结构域,如CD28,以及T细胞的快速增殖、细胞因子分泌和抗凋亡能力。第三代通过CD3-CD28-41BB或CD3-CD28-OX40增强了细胞因子的产生和杀伤能力,最终在第四代中,嵌合抗原受体被认为是导向常见细胞因子介导杀伤的T细胞,这是通过添加白细胞介素-2来根除癌细胞所致。耐药性激活的发生,如细胞因子释放综合征、神经毒性和靶向/脱靶识别,是CAR-T 细胞的难点。美国食品药品监督管理局(FDA)批准了这种CAR-T 细胞治疗在血液肿瘤中的成功应用。
此外,美国和我国是CAR-T 细胞疗法发展的先驱。临床试验已经通过联合疗法取得了显著结果。为了提高T细胞效率,需要针对各种实体瘤采用新策略,以瞄准肿瘤特征并尽量减少CAR-T 细胞的毒性。
Adoptive cell transfer (ACT), a fast and promising new advance in immunotherapy for cancer treatment is the chimeric antigen receptor T-cell therapy with the purpose of programming the immune system to attack tumors. Engineered CAR receptors have developed over time depending on the composition of the four generations in the chimeric antigen receptors. Sufficient interleukin-2 (IL-2) is not generated by CAR-T cells in the first generation to exterminate the cancer cells. The next generation adds a secondary single domain such as CD28 and the rapid multiplication of T cells, secretion of cytokine, and immunity to apoptosis.
The production of cytokine and killing capability was enhanced by CD3 -CD28-41BB or CD3 -CD28-OX40 in the third generation, and finally in the fourth generation, the chimeric antigen receptors are known to be T cells that direct for common cytokine-mediated killing that is caused by the addition of interleukin-2 to eradicate cancer cells.
Onsets of resistant activation, such as cytokine release syndrome, neurological toxicity, and on-target/off-target recognition, are the difficulties in CAR T cells. The Food and Drug Administration (FDA) approved the successes of this chimeric antigen receptor T cell treatment for hematologic tumors.
Moreover, the United States and China are the pioneers in the growth of CAR-T cell therapy. Remarkable results by combination therapies have been created by the clinical trials. To improve T cell efficiency, there is the need to adopt new strategies for various solid tumors to aim at tumor profiles and to minimize toxicity of CAR-T cells.
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