ArticleJournal for immunotherapy of cancer2023
Targeting T-cell malignancies using allogeneic double-negative CD4-CAR-T cells.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Integrated Single Cell Analysis Reveals the Transcriptional Heterogeneity of Mouse Double Negative T Cells.International journal of molecular sciences · 2026Article
- FcεRIγ reinforces double-negative T cell-mediated antibody-dependent cellular cytotoxicity against tumor cells.Journal of molecular cell biology · 2026Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Single-Cell Dissection Reveals Immune Dysregulation After CD5 or CD7-Directed Chimeric Antigen Receptor T-Cell Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.Biology · 2025Review
- Recent advances in universal chimeric antigen receptor T cell therapy.Journal of hematology & oncology · 2025Review
- SOCS1 Protects Acute Myeloid Leukemia against Allogeneic T Cell-Mediated Cytotoxicity.Blood cancer discovery · 2025Article
- Single-cell RNA sequencing of human double-negative T cells reveals a favorable cellular signature for cancer therapy.Journal for immunotherapy of cancer · 2025Article
- Characterization and effective expansion of CD4Molecular therapy. Methods & clinical development · 2025Article
- Modulation of double-negative T cells by Huang-Lian-Jie-Du Decoction attenuates neuroinflammation in ischemic stroke: insights from single-cell transcriptomics.Frontiers in immunology · 2025Article
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Advances in CAR-T-cell therapy in T-cell malignancies.Journal of hematology & oncology · 2024Review
- Broadening the horizon: potential applications of CAR-T cells beyond current indications.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPatients with relapsed/refractory T-cell malignancies have limited treatment options. The use of chimeric antigen receptor (CAR)-T cell therapy for T-cell malignancies is challenging due to possible blast contamination of autologous T-cell products and fratricide of CAR-T cells targeting T-lineage antigens. Recently, allogeneic double-negative T cells (DNTs) have been shown to be safe as an off-the-shelf adoptive cell therapy and to be amendable for CAR transduction. Here, we explore the antitumor activity of allogeneic DNTs against T-cell malignancies and the potential of using anti-CD4-CAR (CAR4)-DNTs as adoptive cell therapy for T-cell malignancies.
methodsHealthy donor-derived allogeneic DNTs were ex vivo expanded with or without CAR4 transduction. The antitumor activity of DNTs and CAR4-DNTs against T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL) were examined using flow cytometry-based cytotoxicity assays and xenograft models. Mechanisms of action were investigated using transwell assays and blocking assays.
resultsAllogeneic DNTs induced endogenous antitumor cytotoxicity against T-ALL and PTCL in vitro, but high doses of DNTs were required to attain therapeutic effects in vivo. The potency of DNTs against T-cell malignancies was significantly enhanced by transducing DNTs with a third-generation CAR4. CAR4-DNTs were manufactured without fratricide and showed superior cytotoxicity against CD4
conclusionsThese results demonstrate that CAR4-DNTs can effectively target T-ALL and PTCL and support allogeneic CAR4-DNTs as adoptive cell therapy for T-cell malignancies.
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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.