智能细菌平台诱导编程死亡配体1溶酶体降解以增强抗瘤免疫力
Shuailin He1, Shuai Zhao1, Xuan Luo1
1State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan 430062, PR China.
International journal of biological macromolecules
|September 4, 2025
概括
提供CXCL12-KN035融合蛋白的工程细菌向瘤,降解PD-L1以减少免疫抑制并抑制癌症生长. 这种新的方法增强了T细胞的活性,
科学领域:
- 癌症学
- 微生物学
- 免疫疗法
背景情况:
- 通过利用瘤微环境 (TME),工程细菌提供向瘤治疗.
- 在TME中,低氧和免疫抑制促进选择性细菌殖民,并降低宿主毒性.
- 目前的疗法往往提供暂时阻塞,需要新的方法.
研究的目的:
- 开发一种新型的细菌疗法,
- 创建一个融合蛋白 (CXCL12-KN035),同时准CXCR7和PD-L1.
- 建立一个以退化为中心的癌症治疗模式.
主要方法:
- 构建了一个低内毒素大肠杆菌表达系统.
- 工程细菌产生CXCL12-KN035融合蛋白.
- 研究了PD-L1内化和降解的机制.
主要成果:
- CXCL12-KN035融合蛋白针对CXCR7和PD-L1,从而诱导PD-L1的降解.
- 在TME中降低免疫抑制.
- 增强瘤特异性T细胞的激活和增殖.
- 在实验模型中显著抑制瘤生长和转移.
结论:
- 表达CXCL12-KN035的工程细菌提供了一个新的治疗策略.
- PD-L1的退化提供了一个超越免疫检查点封锁的新范式.
- 这种方法显示了细菌媒介癌症治疗的巨大潜力.
相关概念视频
Cytotoxic T Cells-mediated Immune Response
1.9K
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...
1.9K
Cells of the Innate Immune Response
3.1K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
3.1K
The Intrinsic Apoptotic Pathway
6.8K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.8K
Autophagic Cell Death
3.5K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.5K
Defense Against Bacterial Pathogens
1.5K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
1.5K
The Extrinsic Apoptotic Pathway
6.6K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.6K


