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:Lymph Node-Targeting Nanotherapy Combined with Photothermal Therapy to Potentiate Chimeric Antigen Receptor-T Cell Treatment of Oral Cancer.
Lymph Node-Targeting Nanotherapy Combined with Photothermal Therapy to Potentiate Chimeric Antigen Receptor-T Cell Treatment of Oral Cancer.
口腔鳞状细胞癌(OSCC)是头颈部最常见的癌症之一。
口腔鳞状细胞癌(OSCC)是头颈部最常见的癌症之一。免疫治疗因其潜在临床获益,已成为转移性 OSCC 的一种有前景的治疗选择;但其效果受免疫抑制性肿瘤微环境(TME)、应答持续时间短和肿瘤浸润不足限制。为克服这些问题,我们开发了光热治疗(PTT)联合嵌合抗原受体(CAR)T 细胞免疫治疗的策略。制备的共轭聚合物纳米颗粒(CPNP)可作为高效近红外二区(NIR-II)光热剂,实现局部 PTT 并诱导强烈免疫原性细胞死亡(ICD)以激活 T 细胞。此外,我们构建了靶向淋巴结的纳米系统 ApoA1@PNPs,以提高体内 CAR-T 细胞生成。研究还设计了黏蛋白1(MUC1)特异性 CAR-T 细胞,以增强肿瘤抗原识别。该联合策略有助于 CAR-T 细胞更有效地到达原发肿瘤部位,并诱导持久的全身免疫。通过应对传统 CAR-T 治疗 OSCC 的主要局限,我们提出的 PTT/CAR-T 综合策略具有潜在治疗价值和临床应用前景,旨在通过改善肿瘤控制提升患者结局。
Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the head and neck. Immunotherapy has emerged as a promising treatment option for metastatic OSCC because of its potential clinical benefits; however, its effectiveness is limited by the immunosuppressive tumor microenvironment (TME), short-lived responses, and poor infiltration. To overcome these issues, we developed a strategy that combines photothermal therapy (PTT) with chimeric antigen receptor (CAR)-T cell immunotherapy. The prepared conjugated polymer nanoparticles (CPNPs) serve as efficient near-infrared-II (NIR-II) photothermal agents, enabling localized PTT and triggering strong immunogenic cell death (ICD) to activate T cells. Moreover, we engineered a lymph node-targeting nanosystem (ApoA1@PNPs) to improve in vivo production of CAR-T cells. Mucin 1 (MUC1)-specific CAR-T cells were designed to enhance tumor antigen recognition. This combined approach helps CAR-T cells reach primary tumor sites more effectively and induces long-lasting systemic immunity. By addressing the main limitations of traditional CAR-T therapy in OSCC, our integrated PTT/CAR-T strategy offers a potential therapeutic approach with significant clinical potential. This dual method aims to improve patient outcomes by achieving better tumor control.
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