肿瘤细胞治疗研究
英文原题：Combining locoregional CAR-T cells, autologous + allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma.
Combining locoregional CAR-T cells, autologous + allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma.
在接受该治疗 3 个月后，将通过瘤内途径给予 CAR-T 细胞（转导 IL13R 2-CAR）。
多形性胶质母细胞瘤（GBM）是一种侵袭性脑部恶性肿瘤，其微环境会限制免疫细胞活性。目前正在研究 CAR-T 细胞治疗癌症，并有报告显示，经鞘内给予 CAR-T 细胞后，多灶性 GBM 可显著消退。本文提出一种治疗 GBM 的三重免疫疗法。首先，保存每位患者的 GBM 肿瘤标本并进行培养，以制备肿瘤裂解物。随后使用具有免疫刺激、抗糖酵解和抗血管生成作用的 levamisole。对免疫系统进行预激后，向 GBM 患者注射其自身肿瘤细胞裂解物及 GBM 细胞系 U251 的裂解物。治疗 3 个月后，通过瘤内途径给予转导 IL13Rα2-CAR 的 CAR-T 细胞。这样，基因修饰和天然免疫细胞可能在深部浸润肿瘤细胞附近相遇，并通过细胞间相互作用发挥更强疗效，进而启动自我维持的循环过程——癌症免疫循环——以清除癌细胞。
Glioblastoma multiforme (GBM) is an aggressive brain malignancy and harbors a microenvironment limiting immune cells activity. CAR-T cells are being tested in the treatment of cancers and there exist reports which demonstrate dramatic regression of multicentric GBMs following intrathecal treatment with CAR-T cells. In this article, a triple approach for immune treatment of GBM is proposed. First, GBM tumor specimens for each patient will be saved and cultured to obtain tumor lysates. Then, levamisole will be applied, which possesses immunostimulating, anti-glycolytic, and anti-angiogenic features. Following priming the immune system, GBM patients will be injected with lysates of their own tumor cells plus lysates from a GBM cell line, U251. After 3 months of this treatment, CAR-T cells (transduced with IL13R 2-CAR ) will be applied via intratumoral approach. As such, genetically-modified and native immunocytes may 'meet' in the vicinity of deeply-invading tumor cells and demonstrate greater efficacy via cell-cell interactions. By this, a self-propagating cyclic process - a cancer-immunity cycle - may be initiated to eradicate cancer cells.
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