ArticleJournal of hematology & oncology2015
AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells.
Article in Journal of hematology & oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Current Role of CAR-T Therapy in Haematological Care.Advances in experimental medicine and biology · 2025Review
- Gene Therapy and Cardiovascular Diseases.Advances in experimental medicine and biology · 2023Article
- Pre-clinical development of a novel CD3-CD123 bispecific T-cell engager using cross-over dual-variable domain (CODV) format for acute myeloid leukemia (AML) treatment.Oncoimmunology · 2021Article
- CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies.Cancers · 2020Review
- Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies.Frontiers in immunology · 2020Review
- Immune targets in the tumor microenvironment treated by radiotherapy.Theranostics · 2019Review
- Hypoxia-Driven Immunosuppressive Metabolites in the Tumor Microenvironment: New Approaches for Combinational Immunotherapy.Frontiers in immunology · 2018Review
- Clinical trials of CAR-T cells in China.Journal of hematology & oncology · 2017Article
- Overcoming the Immunosuppressive Tumor Microenvironment of Hodgkin Lymphoma Using Chimeric Antigen Receptor T Cells.Cancer discovery · 2017Article
- Mesenchymal stromal cells as vehicles of tetravalent bispecific Tandab (CD3/CD19) for the treatment of B cell lymphoma combined with IDO pathway inhibitor D-1-methyl-tryptophan.Journal of hematology & oncology · 2017Article
- New development in CAR-T cell therapy.Journal of hematology & oncology · 2017Review
- Is CD47 an innate immune checkpoint for tumor evasion?Journal of hematology & oncology · 2017Review
- The Natural Antiangiogenic Compound AD0157 Induces Caspase-Dependent Apoptosis in Human Myeloid Leukemia Cells.Frontiers in pharmacology · 2017Article
- CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression.Frontiers in immunology · 2017Article
- Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies.The Journal of clinical investigation · 2016Article
- Immunoprofiling of leukemic stem cells CD34+/CD38-/CD123+ delineate FLT3/ITD-positive clones.Journal of hematology & oncology · 2016Article
- Bispecific antibodies and their applications.Journal of hematology & oncology · 2015Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeukemic stem cells (LSCs) are frequently seen as a cause of treatment failure and relapse in patients with acute myeloid leukemia (AML). Thus, successful new therapeutic strategies for the treatment of AML should aim at eradicating LSCs. The identification of targets on the cell surface of LSCs is getting more and more attention. Among these, CD123, also known as the interleukin-3 (IL3)-receptor α chain, has been identified as a potential immunotherapeutic target due to its overexpression on LSCs in AML as well as on AML blasts, rather than normal hematopoietic stem cells.
methodsWe constructed a CD123-targeted fusion protein antiCD3Fv-⊿IL3, with one binding site for T cell antigen receptor (TCRCD3) and the other for CD123, by recombinant gene-engineering technology. Cysteine residues were introduced into the V domains of the antiCD3Fv segment to enhance its stability by locking the two chains of Fv together with disulfide covalent bonds. The stability and cytotoxicity of the two fusion proteins were detected in vitro and in vivo.
resultsBoth fusion proteins were produced and purified from Escherichia coli 16C9 cells with excellent yields in fully active forms. High-binding capability was observed between these two fusion proteins and human IL3R, leading to the specific lysis of CD123-expressing cell lines KG1a; also, mononuclear cells from primary AML patients were inhibited in a colony forming assay in vitro, presumably by redirecting T lymphocytes in vitro. In addition, they displayed an antileukemic activity against KG1a xenografts in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, especially disulfide-stabilized (ds)-antiCD3Fv-⊿IL3 for its improved stability.
conclusionsThese results suggest that both fusion proteins display the antileukemic activity against CD123-expressing cell lines as well as leukemic progenitors in vitro and in vivo, especially ds-antiCD3Fv-⊿IL3. They could be the promising candidates for future immunotherapy of AML.
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