This is a single-arm study to evaluate the efficacy and safety of CD207 targeted CAR-T cell therapy in relapsed and refractory langerhans cell histiocytosis.

开始日期2022-10-01

申办/合作机构

北京友谊医院

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100 项与 CD207 CAR-T cells(Beijing Friendship Hospital) 相关的临床结果

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100 项与 CD207 CAR-T cells(Beijing Friendship Hospital) 相关的转化医学

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100 项与 CD207 CAR-T cells(Beijing Friendship Hospital) 相关的专利（医药）

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项与 CD207 CAR-T cells(Beijing Friendship Hospital) 相关的文献（医药）

2023-11-02·Immunopharmacology and Immunotoxicology

CD26 CAR-T cells have attenuated mitochondrial and glycolytic metabolic profiling

Article

作者: Zhong, Zhaodong ; Meng, Fankai ; Zou, Ping ; Li, Qing ; Zhu, Xiaoying ; You, Yong ; Zhu, Xiaojian

BACKGROUNDMultiple targets of chimeric antigen receptor T cells (CAR-T cells) are shared expressed by tumor cells and T cells, these self-antigens may stimulate CAR-T cells continuously during the expansion. Persistent exposure to antigens is considered to cause metabolic reprogramming of T cells and the metabolic profiling is critical in determining the cell fate and effector function of CAR-T cells. However, whether the stimulation of self-antigens during CAR-T cell generation could remodel the metabolic profiling is unclear. In this study, we aim to investigate the metabolic characteristics of CD26 CAR-T cells, which expressed CD26 antigens themselves.METHODSThe mitochondrial biogenesis of CD26 and CD19 CAR-T cells during expansion was evaluated by the mitochondrial content, mitochondrial DNA copy numbers and genes involved in mitochondrial regulation. The metabolic profiling was investigated by the ATP production, mitochondrial quality and the expression of metabolism-related genes. Furthermore, we assessed the phenotypes of CAR-T cells through memory-related markers.RESULTSWe reported that CD26 CAR-T cells had elevated mitochondrial biogenesis, ATP production and oxidative phosphorylation at early expansion stage. However, the mitochondrial biogenesis, mitochondrial quality, oxidative phosphorylation and glycolytic activity were all weakened at later expansion stage. On the contrary, CD19 CAR-T cells did not exhibit such characteristics.CONCLUSIONCD26 CAR-T cells showed distinctive metabolic profiling during expansion that was extremely unfavorable to cell persistence and function. These findings may provide new insights for the optimization of CD26 CAR-T cells in terms of metabolism.

2022-08-16·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy

1区 · 综合性期刊

Article

作者: Garcia, K. Christopher ; O’Hearn, James ; Saravanakumar, Supraja ; Cohen, Joseph R. ; Starr, Renate ; Brown, Christine E. ; Yang, Xin ; Moraga, Ignacio ; Stern, Lawrence A. ; Gholamin, Sharareh ; Salvary, Vanessa ; Hibbard, Jonathan C. ; Shepphird, Jennifer K. ; Aguilar, Brenda ; Kalbasi, Anusha

IL13Rα2 is an attractive target due to its overexpression in a variety of cancers and rare expression in healthy tissue, motivating expansion of interleukin 13 (IL13)–based chimeric antigen receptor (CAR) T cell therapy from glioblastoma into systemic malignancies. IL13Rα1, the other binding partner of IL13, is ubiquitously expressed in healthy tissue, raising concerns about the therapeutic window of systemic administration. IL13 mutants with diminished binding affinity to IL13Rα1 were previously generated by structure-guided protein engineering. In this study, two such variants, termed C4 and D7, are characterized for their ability to mediate IL13Rα2-specific response as binding domains for CAR T cells. Despite IL13Rα1 and IL13Rα2 sharing similar binding interfaces on IL13, mutations to IL13 that decrease binding affinity for IL13Rα1 did not drastically change binding affinity for IL13Rα2. Micromolar affinity to IL13Rα1 was sufficient to pacify IL13-mutein CAR T cells in the presence of IL13Rα1-overexpressing cells in vitro. Interestingly, effector activity of D7 CAR T cells, but not C4 CAR T cells, was demonstrated when cocultured with IL13Rα1/IL4Rα-coexpressing cancer cells. While low-affinity interactions with IL13Rα1 did not result in observable toxicities in mice, in vivo biodistribution studies demonstrated that C4 and D7 CAR T cells were better able to traffic away from IL13Rα1+ lung tissue than were wild-type (WT) CAR T cells. These results demonstrate the utility of structure-guided engineering of ligand-based binding domains with appropriate selectivity while validating IL13-mutein CARs with improved selectivity for application to systemic IL13Rα2-expressing malignancies.

2022-03-14·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

[Functional investigation of chimeric antigen receptor T cells targeting LMP1 antigen].

Article

作者: Rao, Q ; He, H Z ; Wang, M ; Wang, J X ; Xing, Y Y ; Xing, H Y ; Xu, Y X ; Tian, Z ; Zhang, Y ; Tang, K J

目的： 制备一种靶向LMP1抗原的嵌合抗原受体T细胞（CAR-T细胞），研究其对EB病毒（EBV）阳性淋巴瘤的免疫治疗作用。 方法： 应用分子克隆技术构建二代LMP1 CAR表达质粒，通过慢病毒包装体系包装病毒后感染人T细胞，获得LMP1 CAR-T细胞，体外实验验证LMP1 CAR-T细胞对感染EBV后的LMP1阳性淋巴瘤细胞的特异性细胞毒性作用。 结果： ①LMP1蛋白表达于EBV阳性的淋巴瘤细胞表面；②成功构建了二代LMP1 CAR慢病毒载体，感染人T细胞，获取LMP1 CAR-T细胞，感染效率大于80%；③LMP1 CAR-T细胞可特异性杀伤LMP1阳性淋巴瘤细胞，当效靶比按4∶1共培养48 h后，LMP1 CAR-T细胞对Raji细胞的杀伤作用增强，对Ramos细胞无明显杀伤作用；④与LMP1阳性淋巴瘤细胞按1∶1共培养5 h后，LMP1 CAR-T细胞处理组CD107a(+) T细胞比例显著高于Vector-T细胞组[（13.25±2.94）%对（1.55±0.05）%，t＝3.972，P＝0.017]，脱颗粒效果增强；⑤与LMP1阳性淋巴瘤细胞共培养后，LMP1 CAR-T细胞组CD69(+)、CD25(+) T细胞比例显高于Vector-T细胞组[（7.40±0.41）%对（3.48±0.47）%，t＝6.268，P＝0.003；（73.00±4.73）%对（57.67±2.60）%，t＝2.842，P＝0.047]，活化效应增强。⑥与LMP1阳性淋巴瘤细胞共培养后，LMP1 CAR-T细胞组细胞因子分泌增强，高于Vector-T细胞组[IFN-γ：（703±73）ng/L对（422±87）ng/L，t＝2.478，P＝0.068；TNF-α：（215±35）ng/L对（125±2）ng/L，t＝2.536，P＝0.064]。 结论： 该研究证实EBV阳性淋巴瘤细胞表面可特异表达LMP1蛋白，成功构建了LMP1 CAR慢病毒载体并感染人T细胞，成功获得LMP1 CAR-T细胞。体外实验证实：与LMP1阳性淋巴瘤细胞共培养后，LMP1 CAR-T细胞脱颗粒效果增强，活化效应增强，高效分泌细胞因子，可特异杀伤LMP1阳性淋巴瘤细胞，具有潜在的临床应用前景。.

100 项与 CD207 CAR-T cells(Beijing Friendship Hospital) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
郎格罕细胞组织细胞增生症	临床1期	中国	Beijing Boren Hospital	2022-10-01
郎格罕细胞组织细胞增生症	临床1期	中国	北京友谊医院	2022-10-01