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:HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo.
我们的研究表明,HER2 CAR-T 细胞是治疗 GBM 的一种新兴免疫疗法。
胶质母细胞瘤(GBM)是成人最常见、侵袭性最强的原发性恶性脑肿瘤。目前 GBM 治疗包括手术切除、放疗和化疗,这些治疗主要减缓癌症生长并减轻症状,5 年生存率不超过 10%。嵌合抗原受体(CAR)T 细胞疗法是一种新型细胞免疫疗法,在治疗恶性肿瘤方面取得了显著进展。GBM 中人表皮生长因子受体 2(HER2)过表达,可能成为 GBM 治疗的潜在靶点。本研究构建了靶向 GBM HER2 抗原的第三代 CAR-T 细胞。HER2-CAR-T 在体外和体内均显示出有效抗肿瘤活性。体外实验中,HER2 特异性 CAR-T 对 GBM 细胞具有强效细胞毒性并可分泌细胞因子;随着效靶比升高,抗 HER2 CAR-T 的细胞毒性也增强。瘤周注射抗 HER2 CAR-T 可成功抑制体内肿瘤进展。此外,与静脉注射相比,瘤周给药在治疗 GBM 方面效果更好。综上,本研究显示 HER2 CAR-T 是一种新兴的 GBM 免疫治疗方法。
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR) T-cell therapy is a new class of cellular immunotherapy that has made great progress in treating malignant tumors. Human epidermal growth factor receptor 2 (HER2) is overexpressed in GBM and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.
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