Evidence map›Paper›PMID 40719826›Full record

ArticleClinical and experimental medicine2025

A bi-specific CAR-T cell therapy targeting CD19 and CD22 in relapsed or refractory B-ALL.

Qiuling Ma, Runhong Wei, Qingming Wang, Songfu Jiang, Yi Wu, Chao Min, Shufang Guo, Yu Zhang, Xiaohong Sun, Haigang Wu and 4 more

Registry-linked trialAbstract readClinical Trial, Phase I
In one paragraph

Article in Clinical and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04303520 (A Phase I Clinical Trial of T-Cells Targeting CD19 and CD22 for Subjects With CD19-positive Acute Lymphoblastic Leukemia), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04303520 phase1unknown statusnot on this map

A Phase I Clinical Trial of T-Cells Targeting CD19 and CD22 for Subjects With CD19-positive Acute Lymphoblastic Leukemia

TypeinterventionalSponsorThe Second Affiliated Hospital of Henan University of Traditional Chinese MedicineRan2018 to 2021Enrolled20ConditionsCD19-positive ALLArmsanti-CD19/CD22 CAR-T cells, Fludarabine, Cyclophosphamide
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. CD22 as a Target for Hematological Malignancies and Autoimmune Diseases.International journal of molecular sciences · 2026
    Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Qiuling MaThe Second School of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, China.
Runhong WeiDepartment of Hematology, Henan Province Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital, Henan University of Chinese Medicine), Institute of Hematology, Henan University of Chinese Medicine, Zhengzhou, 450002, Henan Province, China.
Qingming WangThe 2nd Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Hematological Diseases, Nanchang, 330006, Jiangxi Province, China.
Songfu JiangDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Yi WuDepartment of Hematology, Henan Province Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital, Henan University of Chinese Medicine), Institute of Hematology, Henan University of Chinese Medicine, Zhengzhou, 450002, Henan Province, China.
Chao MinThe 2nd Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Hematological Diseases, Nanchang, 330006, Jiangxi Province, China.
Shufang GuoThe 2nd Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Hematological Diseases, Nanchang, 330006, Jiangxi Province, China.
Yu ZhangDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Xiaohong SunDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
Haigang WuSchool of Life Sciences, Henan University, Kaifeng City, 475000, China.
Xuedong SunHrain Biotechnology Co., Ltd., Shanghai, 200030, China.
Fang XiangHrain Biotechnology Co., Ltd., Shanghai, 200030, China.
Mingxing XiaoHrain Biotechnology Co., Ltd., Shanghai, 200030, China.
Zhi ChengThe Second School of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, China. chzhi63@163.com.

Funding

Government-funded Project on Traditional Chinese Medicine in Henan Province of China 2024ZY1010Natural Science Foundation of Henan Province of China 222300420487The Scientific and technological project in Henan Province of China 222102310353
6 · The paper itself

Abstract

CAR-T therapies targeting either CD19 or CD22 have shown significant promise for treating relapsed or refractory B-lineage acute lymphoblastic leukemia (r/r B-ALL). However, a common limitation is the high frequency of antigen loss, which leads to r/r B-ALL progression. To overcome progression caused by antigen loss, bi-specific CAR-T immunotherapies targeting both CD19 and CD22 may offer enhanced efficacy in eliminating r/r B-ALL and preventing relapse by hindering leukemia cell proliferation. In this study, we present both pre-clinical and clinical findings from an ongoing trial (NCT04303520) assessing the therapeutic efficacy of the CD19-CD22 bi-specific CAR-T therapy for r/r B-ALL patients. Pre-clinical data from animal models reveal that CD19-CD22 CAR-T cells effectively induce cytotoxicity, thus suppressing B-ALL cell proliferation. Notably, this dual-targeted approach outperforms single-target CAR-T treatments. From the Phase I trial encompassing 35 participants, 37.1% (13 out of 35 patients) experienced cytokine release syndrome, with only a single case of Grade III   severity. Importantly, no neurotoxicity episodes were recorded post CD19-CD22 CAR-T administration. Common adverse events included hematological, gastrointestinal, and nutrition-related disturbances. B-ALL patients undergoing stem cell transplantation in tandem with CAR-T therapy exhibited a pronounced improvement in overall survival compared to those treated solely with CAR-T. The median overall survival duration was 21.49 ± 4.4 months (95% CI: 14.31-31.40 months), meanwhile one-year PFS and OS are 0.37 (95% CI, 0.21-0.49) and 0.62 (95% CI: 0.52-0.71), respectively. Clinical monitoring did not identify significant side effects associated with the CD19-CD22 regimen. To monitor the inflammation-associated factors accompanying CAR-T therapy, the peak value of CAR DNA copies was reached around Day 10, accompanied by a similar trend in the levels of inflammatory factors, including IFN-γ, Granzyme B, IL-6, and CRP. Collectively, our data advocate for the potential role of bi-specific CD19-CD22 CAR-T therapy in addressing r/r B-ALL. Trial registration number ClinicalTrials.gov (No. NCT04303520).

Indexed as

Antigens, CD19Immunotherapy, AdoptivePrecursor B-Cell Lymphoblastic Leukemia-LymphomaReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2AdolescentAdultAnimalsChildCytokine Release SyndromeFemaleHumansMaleMiceMiddle AgedT-LymphocytesAntigens, CD19CD19 molecule, humanCD22 protein, humanReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2Bi-specific CARCD19CD22Chimeric antigen receptor T cellsR/r B-ALL

Identifiers

PMID40719826
PMCPMC12304051

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.