ArticlemAbs
A single-chain triplebody with specificity for CD19 and CD33 mediates effective lysis of mixed lineage leukemia cells by dual targeting.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- Trial
- Oncolytic adenoviruses encoding bispecific T cell engagers or a novel trispecific T cell engager for dual-targeting of c-MET and EGFR.Molecular therapy. Oncology · 2026Article
- Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager.Molecules (Basel, Switzerland) · 2024Article
- When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy.Theranostics · 2023Review
- Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer.Oncoimmunology · 2022Article
- Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future.Stem cell research & therapy · 2021Review
- A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy.Cancer immunology research · 2021Article
- Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions.Frontiers in immunology · 2020Review
- Review
- Natural killer cells unleashed: Checkpoint receptor blockade and BiKE/TriKE utilization in NK-mediated anti-tumor immunotherapy.Seminars in immunology · 2017Review
- Acute myeloid leukemia targets for bispecific antibodies.Blood cancer journal · 2017Review
- Article
- Antigen Loss Variants: Catching Hold of Escaping Foes.Frontiers in immunology · 2017Article
- Triplebody Mediates Increased Anti-Leukemic Reactivity of IL-2 Activated Donor Natural Killer (NK) Cells and Impairs Viability of Their CD33-Expressing NK Subset.Frontiers in immunology · 2017Article
- CD19-specific triplebody SPM-1 engages NK and γδ T cells for rapid and efficient lysis of malignant B-lymphoid cells.Oncotarget · 2016Article
- Dual-targeting triplebody 33-3-19 mediates selective lysis of biphenotypic CD19+ CD33+ leukemia cells.Oncotarget · 2016Article
- Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies.Computational and structural biotechnology journal · 2016Review
- Generation of BiKEs and TriKEs to Improve NK Cell-Mediated Targeting of Tumor Cells.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward?Antibodies (Basel, Switzerland) · 2015Review
- Update on antigen-specific immunotherapy of acute myeloid leukemia.Current hematologic malignancy reports · 2015Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A single-chain triplebody (sctb) 33-ds16-ds19 comprising two distal single-chain Fv fragments (scFvs) specific for the lymphoid antigen CD19 and the myeloid antigen CD33 flanking a central scFv specific for CD16, which is the low affinity Fc-receptor (FcγRIII) present on natural killer cells and macrophages, was produced and its properties were investigated. CD33 and CD19 in combination are present on acute leukemiablasts with mixed lineage phenotype, but not on normal human hematopoietic cells. For comparison, two bispecific scFvs (bsscFvs), ds19-ds16 and 33-ds16, with monovalent binding to CD19 and CD33, respectively, were also studied. The sctb 33-ds16-ds19 specifically interacted with all 3 antigens. On the antigen double-positive cell line BV-173, the sctb bound with 2-fold greater avidity than bsscFv ds19-ds16 (KD = 21 vs. 42 nM) and with 1.4-fold greater avidity than bsscFv 33-ds16 (KD = 29 nM). All 3 fusion proteins had similar affinity for CD16 and sufficient thermic stability in human serum. In antibody-dependent cellular cytotoxicity (ADCC) reactions with human mononuclear cells as effectors, the sctb promoted lysis of BV-173 cells at 23-fold lower concentrations than bsscFv ds19-ds16 and at 1.4-fold lower concentrations than bsscFv 33-ds16. The sctb also mediated potent ADCC of the antigen double-positive mixed lineage leukemia cell line SEM, and the half-maximal concentration EC50 for BV-173 cells was 7 pM. Therefore, CD19 and CD33 are present on the surface of these leukemic cell lines such that they can be connected by a single sctb molecule, permitting the recruitment of NK cells via CD16 and tumor cell lysis.
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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.