This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19)

开始日期2020-09-11

申办/合作机构

The University of California, San Francisco

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100 项与 anti-CD19 CAR-T cells(University of California) 相关的临床结果

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100 项与 anti-CD19 CAR-T cells(University of California) 相关的转化医学

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100 项与 anti-CD19 CAR-T cells(University of California) 相关的专利（医药）

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项与 anti-CD19 CAR-T cells(University of California) 相关的文献（医药）

2024-12-01·Computational and Structural Biotechnology Journal

In silico and in vivo analysis reveal impact of c-Myc tag in FMC63 scFv-CD19 protein interface and CAR-T cell efficacy

Article

作者: Lourenzoni, Marcos Roberto ; Batista-Silva, Leonardo Ribeiro ; Abdo, Luiza ; Correia, Eduardo Mannarino ; Aragão, Emmanuel Arthur Albuquerque ; Bonamino, Martín Hernán ; Lima, Ana Julia Ferreira ; de Oliveira Andrade, Clara ; Hajdu, Karina Lobo

Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv's structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.

2024-11-01·Rheumatology

Comment on: Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T cells after failure of several B-cell depleting antibodies

Article

作者: Schneider, Udo ; Krusche, Martin ; Stenzel, Werner ; Ruffer, Nikolas

2024-08-01·Journal of Zhejiang University-SCIENCE B

Waldenström macroglobulinemia: a challenging case treated with anti-CD19 CAR-T cell therapy

Article

作者: Yang, Yang ; He, Jingsong ; Cai, Zhen ; Hu, Yongxian ; Gu, Xiaolin

华氏巨球蛋白血症（WM）是一种罕见的小淋巴细胞、浆细胞样淋巴细胞和浆细胞肿瘤，会累及骨髓，甚至累及淋巴结和脾，通常与克隆性IgM球蛋白血症相关。尽管WM通常伴有惰性临床病程，但却无法治愈。本研究报告了一个具有挑战性的WM案例。该患者在化疗、免疫治疗和布鲁顿酪氨酸激酶（BTK）抑制剂治疗后出现复发/难治性病变，并累及髓外，但在CD19定向嵌合抗原受体T（CAR-T）细胞治疗后病情得到改善。此外，我们还回顾了文献中报道的CAR-T细胞治疗WM病例。本案例中的患者已接受一年多的随访，其病情仍保持良好的部分缓解状态，这表明CAR-T细胞疗法具有作为复发/难治性WM替代方案的潜力。人们迫切希望进行更大规模的临床研究来评估这种疗法的有效性和安全性。.

100 项与 anti-CD19 CAR-T cells(University of California) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
非霍奇金淋巴瘤	临床1期	美国	The V Foundation	2024-10-30
伯基特淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11
滤泡性淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11
淋巴浆细胞性淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11
套细胞淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11
纵隔大b细胞淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11
难治性非霍奇金淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11
小淋巴细胞淋巴瘤	临床1期	美国	The University of California, San Francisco	2020-09-11