正在进行的试验:对表达EPHB4受体 (CARTiEr) 的恶性固体瘤进行非病毒基因修饰的CAR- T细胞治疗的I期研究
Chikako Funasaka1,2, Yoichi Naito1,2,3, Hitomi Kubota4
1Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Frontiers in oncology
|August 22, 2025
概括
AP8901 CAR- T细胞治疗向表达EPHB4的固体瘤. 这一第一阶段的研究旨在评估它在患有尤宁肉瘤或其他转移性固体瘤的患者的安全性和有效性,目的是防止T细胞耗尽.
科学领域:
- 癌症学
- 免疫疗法
- 细胞疗法
背景情况:
- 埃弗林B型受体4 (EPHB4) 在各种恶性瘤中过度表达,包括骨和软组织瘤.
- AP8901 CAR- T细胞治疗旨在通过利用修饰的以林B2配体来向表达EPHB4的瘤细胞.
- 开发中使用了piggyBac转体和转基因料细胞来稳定CAR表达和预防T细胞枯竭.
研究的目的:
- 评估AP8901的安全性,耐受性,药理动力学和初步抗瘤活性.
- 在患有尤宁肉瘤或表达EPHB4的其他固体瘤的患者中评估AP8901.
- 为这种新型CAR-T细胞治疗在固体瘤中的临床应用提供证据.
主要方法:
- 单中心,单臂,剂量升级的第一阶段临床试验.
- 静脉注射一次剂量的AP8901.
- 纳入标准:经组织学诊断的尤金瘤或转移/复发的固体瘤,EPHB4表达 (≥1%),ECOG 0-1,存活时间≥3个月.
主要成果:
- AP8901在临床前模型中显示出治疗效果和耐受性 (患有肌肉瘤的小鼠).
- 这项研究旨在提供初步的人体安全性和疗效数据.
- 将收集药物动力学/药物动力学数据以了解AP8901的体内行为.
结论:
- 在治疗EPHB4阳性固体瘤方面,CAR- T细胞疗法显得有前途.
- 治疗的设计旨在克服T细胞耗尽,可能导致持续的抗瘤作用.
- 这一第一阶段的研究对于确定AP8901的安全性和潜在的临床效用至关重要.
相关概念视频
00:59Gene Therapy
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
02:57Targeted Cancer Therapies
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 specific...
There are several types of targeted therapies against specific...
01:27Tumor Immunotherapy
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.