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| Status |
Public on Sep 08, 2022 |
| Title |
Efficacy-enhanced anti-CD7 universal chimeric antigen receptor-T cell therapy for relapsed/refractory CD7-positive hematological malignancies: A phase I clinical study |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chimeric antigen receptor-T cell (CAR-T) therapy in T cell malignancies faces fratricide, T cell aplasia, and product contamination. We developed an universal anti-CD7 CAR-T cells in which TRAC, CD7 and HLA-II were disrupted, while E-cadherin (a NK cell inhibitory molecule) was introduced, to mitigate graft versus host disease (GvHD), fratricide and rejection. Furthermore, we designed a subtle receptor, bbzg-CAR, comprising not only conventional domains (anti-CD7 scFv, 4-1BB co-stimulatory domain, and CD3ζ signaling domain), but also the intracellular domain of common γ chain. Bbzg-CAR-T exerted anti-tumor effects superior to those of conventional universal CAR-T cells. In adoptive therapy for relapsed/refractory (r/r) patients, no dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade≥3) was observed. Nine patients (82%) showed objective response with, complete response rates of 75% and 33.3% in r/r leukemia and lymphoma respectively. Preliminary safety and efficacy of this universal CAR-T product was achieved in CD7+ malignancies.
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| Overall design |
Single-cell RNA analysis were performed in RD13-01 product (batch number C20201001) and PBMCs from patient 5 at day 14 and day 19 post RD13-01 infusion.
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| Contributor(s) |
Huang H, Hu Y, Ren J, Zhou Y |
| Citation(s) |
36151216 |
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| Submission date |
Dec 22, 2021 |
| Last update date |
Dec 08, 2022 |
| Contact name |
He Huang |
| E-mail(s) |
huanghe@zju.edu.cn
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| Organization name |
the First Affiliated Hospital, Zhejiang University School of Medicine
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| Street address |
79 Qingchun Rd., Shangcheng District, Hangzhou
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| City |
Hangzhou |
| ZIP/Postal code |
310000 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA791547 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE192453_RAW.tar |
82.7 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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