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异体和自体抗 CD7 CAR-T 细胞疗法治疗复发或难治性 T 细胞恶性肿瘤。

Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies.

机构信息

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.

出版信息

Blood Cancer J. 2023 Apr 25;13(1):61. doi: 10.1038/s41408-023-00822-w.


DOI:10.1038/s41408-023-00822-w
PMID:37095094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10125858/
Abstract

Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1-2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1-2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7-14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.

摘要

嵌合抗原受体 T(CAR-T)疗法在 T 细胞恶性肿瘤中的应用仍在研究中。CD7 是 T 细胞恶性肿瘤的理想靶点,但也在正常 T 细胞上表达,这可能导致 CAR-T 细胞自相残杀。使用内质网滞留的供体来源抗 CD7 CAR-T 细胞已在 T 细胞急性淋巴细胞白血病(ALL)患者中显示出疗效。在这里,我们开展了一项 I 期临床试验,以探索自体和异体抗 CD7 CAR-T 疗法在 T 细胞 ALL 和淋巴瘤中的差异。10 名患者接受了治疗,其中 5 名接受了自体 CAR-T 治疗。未观察到剂量限制毒性或神经毒性。7 名患者发生 1-2 级细胞因子释放综合征,1 名患者发生 3 级。2 名患者发生 1-2 级移植物抗宿主病。7 名患者骨髓浸润,其中 100%在一个月内达到完全缓解,微小残留病阴性。五分之二的患者获得髓外或结外缓解。中位随访时间为 6 个月(范围 2.7-14 个月),未进行桥接移植。接受异体 CAR-T 细胞治疗的患者缓解率更高,复发率更低,CAR-T 存活时间更长。异体 CAR-T 细胞似乎是 T 细胞恶性肿瘤患者的更好选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/3072af907c9f/41408_2023_822_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/17c04a5031cb/41408_2023_822_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/d119765f6316/41408_2023_822_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/2ed3be94325e/41408_2023_822_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/5c4c0ac63b5e/41408_2023_822_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/3072af907c9f/41408_2023_822_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/17c04a5031cb/41408_2023_822_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/d119765f6316/41408_2023_822_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/2ed3be94325e/41408_2023_822_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/5c4c0ac63b5e/41408_2023_822_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10125985/3072af907c9f/41408_2023_822_Fig5_HTML.jpg

相似文献

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本文引用的文献

[1]
Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study.

Cell Res. 2022-11

[2]
Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia.

Front Immunol. 2022

[3]
Expanding anti-CD38 immunotherapy for lymphoid malignancies.

J Exp Clin Cancer Res. 2022-6-28

[4]
Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial.

Blood. 2022-7-28

[5]
Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma.

Clin Cancer Res. 2022-7-1

[6]
T cells expressing CD5/CD7 bispecific chimeric antigen receptors with fully human heavy-chain-only domains mitigate tumor antigen escape.

Signal Transduct Target Ther. 2022-3-25

[7]
A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma.

J Hematol Oncol. 2021-10-9

[8]
CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity.

J Hematol Oncol. 2021-10-9

[9]
Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw. 2021-9-20

[10]
Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells.

Blood. 2021-12-16

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