ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Characterization of a bispecific FLT3 X CD3 antibody in an improved, recombinant format for the treatment of leukemia.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Review
- Generation and preclinical characterization of a novel bispecific CD19-TCRgammadelta antibody for the treatment of B cell acute lymphoblastic leukemia.Frontiers in immunology · 2026Article
- Expression and Prognostic Value of a Novel B7-H3 (CD276) Antibody in Acute Myeloid Leukemia.Cancers · 2024Article
- Induction of NK cell reactivity against acute myeloid leukemia by Fc-optimized CD276 (B7-H3) antibody.Blood cancer journal · 2024Article
- Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3).Frontiers in oncology · 2024Article
- Targeting GD2 after allogeneic SCT: effector cell composition defines the optimal use of ch14.18 and the bispecific antibody construct NG-CU (GD2-CD3).Cancer immunology, immunotherapy : CII · 2023Article
- Review
- An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Therapeutic Advances in Immunotherapies for Hematological Malignancies.International journal of molecular sciences · 2022Review
- Shortened Hinge Design of Fab x sdAb-Fc Bispecific Antibodies Enhances Redirected T-Cell Killing of Tumor Cells.Biomolecules · 2022Article
- A novel IgG-based FLT3xCD3 bispecific antibody for the treatment of AML and B-ALL.Journal for immunotherapy of cancer · 2022Article
- FLT3-ITD transduces autonomous growth signals during its biosynthetic trafficking in acute myelogenous leukemia cells.Scientific reports · 2021Article
- CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies.Cancers · 2021Article
- Strategies targeting FLT3 beyond the kinase inhibitors.Pharmacology & therapeutics · 2021Review
- BiTEs, DARTS, BiKEs and TriKEs-Are Antibody Based Therapies Changing the Future Treatment of AML?Life (Basel, Switzerland) · 2021Review
- An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer.EMBO molecular medicine · 2021Article
- Review
- Article
- Tocilizumab, but not dexamethasone, prevents CRS without affecting antitumor activity of bispecific antibodies.Journal for immunotherapy of cancer · 2020Article
- An Optimized Full-Length FLT3/CD3 Bispecific Antibody Demonstrates Potent Anti-leukemia Activity and Reversible Hematological Toxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FLT3 is a receptor-tyrosine-kinase that is expressed on leukemic cells of the myeloid and lymphoid lineage rather specifically. We here report on the construction and selection of bispecific FLT3 X CD3 antibodies in a new recombinant format, termed Fabsc, that resembles the normal antibody structure more closely than the well-established bispecific single chain (bssc)-format. Our preferred antibody, which emerged from an initial selection procedure utilizing different FLT3- and CD3-antibodies, contains the FLT3-antibody 4G8 and the CD3-antibody UCHT1. The 4G8 X UCHT1 Fabsc-antibody was found to be superior to a bssc-antibody with identical specificities with respect to (i) affinity to the target antigen FLT3, (ii) production yield by transfected cells, and (iii) the diminished formation of aggregates. T-cell activation in the presence and absence of cultured leukemic cells and killing of these cells was comparable for both molecules. In addition, the 4G8 X UCHT1 Fabsc-antibody was found to induce T-cell activation and efficient killing of leukemic blasts in primary peripheral blood mononuclear cell (PBMC) cultures of acute myeloid leukemia (AML) patients. In these experiments, the bispecific molecule was clearly superior to an Fc-optimized monospecific FLT3-antibody described previously, indicating that within PBMC of AML patients the recruitment of T cells is more effective than that of natural killer cells.
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