决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:New therapeutics for soft tissue sarcomas: Overview of current immunotherapy and future directions of soft tissue sarcomas.
软组织肉瘤是一种罕见且侵袭性强的疾病,转移率为 40% 至 50%。
软组织肉瘤罕见且侵袭性强,转移率约40%至50%。手术、放疗和化疗效果有限,促使研究者探索新型免疫疗法。抗CTLA-4和抗PD-1等免疫检查点抑制剂在部分组织学亚型中显示应答;免疫治疗与化疗、酪氨酸激酶抑制剂或放疗联合也有一定效果。软组织肉瘤通常被视为“冷”肿瘤,过继细胞疗法正被积极研究以增强免疫应答。靶向NY-ESO-1、MAGE-A4等癌睾抗原的基因改造TCR疗法已在部分患者中产生持久应答,尤其是滑膜肉瘤;早期HER2 CAR-T试验也使部分患者疾病稳定。未来CAR-T或可在软组织肉瘤中找到更特异靶点并实现可靠应答。及时识别T细胞诱发的CRS并以激素等免疫抑制治疗至关重要。进一步认识免疫亚型和生物标志物将促进治疗进展。
Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a 'cold', non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.
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