ArticleGene therapy2022
Thrombopoietin-based CAR-T cells demonstrate in vitro and in vivo cytotoxicity to MPL positive acute myelogenous leukemia and hematopoietic stem cells.
Article in Gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.Frontiers in immunology · 2022Pooled it
- Antimetabolites synergize with non-genotoxic antibody drug conjugate conditioning in hematopoietic stem cell lentiviral gene therapy.Molecular therapy. Advances · 2026Article
- Prospects of Chimeric Antigen Receptor T-Cell Therapy in Myelofibrosis: From Immunopathogenesis to Therapeutic Strategies.Cancers · 2026Review
- MicroRNA-142 improves IL1RAP CAR-T cell activity in acute myeloid leukemia.Journal of hematology & oncology · 2025Article
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.International journal of molecular sciences · 2025Review
- Development of multivalent CAR T cells as dual immunotherapy and conditioning agents.Molecular therapy. Oncology · 2025Article
- Next generation targeted non-genotoxic conditioning for hematopoietic stem cell and hematopoietic stem cell-based gene therapy.Frontiers in immunology · 2025Review
- Mutated Flt3Lg Provides Reduced Flt3 Recycling Compared to Wild-Type Flt3Lg and Retains the Specificity of Flt3Lg-Based CAR T-Cell Targeting in AML Models.International journal of molecular sciences · 2023Article
- Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia.Frontiers in immunology · 2023Article
- Tumor buster - where will the CAR-T cell therapy 'missile' go?Molecular cancer · 2022Review
- Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.Signal transduction and targeted therapy · 2022Review
- Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
While targeting CD19+ hematologic malignancies with CAR T cell therapy using single chain variable fragments (scFv) has been highly successful, novel strategies for applying CAR T cell therapy with other tumor types are necessary. In the current study, CAR T cells were designed using a ligand binding domain instead of an scFv to target stem-like leukemia cells. Thrombopoietin (TPO), the natural ligand to the myeloproliferative leukemia protein (MPL) receptor, was used as the antigen binding domain to engage MPL expressed on hematopoietic stem cells (HSC) and erythropoietic and megakaryocytic acute myeloid leukemias (AML). TPO-CAR T cells were tested in vitro against AML cell lines with varied MPL expression to test specificity. TPO-CAR T cells were specifically activating and cytotoxic against MPL+ leukemia cell lines. Though the TPO-CAR T cells did not extend survival in vivo, it successfully cleared the MPL+ fraction of leukemia cells. As expected, we also show the TPO-CAR is cytotoxic against MPL expressing bone marrow compartment in AML xenograft models. The data collected demonstrate preclinical potential of TPO-CAR T cells for stem-like leukemia through assessment of targeted killing of MPL+ cells and may facilitate subsequent HSC transplant under reduced intensity conditioning regimens.
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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.