卡尔-T细胞的代谢重编程:癌症免疫治疗的新前沿
1Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Frontiers in immunology
|December 5, 2025
概括
在制造过程中重编程化学抗原受体 (CAR) T 细胞代谢,提高了它们对固体瘤的持久性和有效性. 这涉及优化免疫代谢和表观遗传调节,以创造更有弹性的CAR T细胞用于癌症治疗.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 代谢工程是代谢工程.
背景情况:
- 化学抗原受体 (CAR) T细胞疗法在血液癌症中表现有前途,但由于瘤微环境,在固体瘤中面临挑战.
- 卡特-T细胞功能障碍,疲劳和有限的持续性与瘤微环境中的代谢适应性不佳有关.
研究的目的:
- 审查免疫代谢和表观遗传学在调节T细胞功能和命运中的作用.
- 强调在制造过程中重新编程CAR T细胞代谢的策略,以提高对固体瘤的疗效.
主要方法:
- 分析T细胞分化,代谢状态和表观遗传修饰之间的相互作用.
- 在ex vivo制造过程中对代谢干预措施的审查,包括糖解抑制剂和PI3K/Akt/mTOR途径,营养优化和细胞因子工程等.
主要成果:
- 调节CAR T细胞代谢的ex vivo可以促进分化成具有增强抗瘤活性的记忆表型 (Tscm,Tcm).
- 代谢干预措施,如向糖解或使用PI3K/Akt/mTOR抑制剂,有利于氧化酸化 (OXPHOS),促进记忆表型.
- 在制造过程中优化营养素和细胞因子选择可以改善CAR T细胞的持久性和耐耗性.
结论:
- 代谢工程,加上在CAR T细胞制造过程中的表观遗传调节,对于开发强效和持久的CAR T细胞产品至关重要.
- 这种方法具有显著的潜力,可以扩大CAR T细胞治疗以治疗固体瘤和其他具有挑战性的恶性瘤.
相关概念视频
01:27Tumor Immunotherapy
1.7K
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.
1.7K
02:57Targeted Cancer Therapies
8.6K
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...
8.6K
02:50Combination Therapies and Personalized Medicine
5.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.9K
02:53Adaptive Mechanisms in Cancer Cells
6.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K