ArticleBlood2017
An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Bispecific Antibodies: From Research to Clinical Application.Frontiers in immunology · 2021Pooled it
- A Simple-to-Use Nomogram for Predicting Survival in Children with Acute Myeloid Leukemia.BioMed research international · 2021Trial
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- CLL-1: An emerging target for immunotherapy in acute myeloid leukemia.Annals of hematology · 2026Review
- Translational potential of γδ T cells in hematologic diseases: from immunobiology to therapeutic innovation.Frontiers in immunology · 2026Review
- Article
- Article
- Chimeric PRR T-cell-engager targeting cell surface β-1,3-glucan for invasive candidiasis.PLoS pathogens · 2025Article
- From Molecular Precision to Clinical Practice: A Comprehensive Review of Bispecific and Trispecific Antibodies in Hematologic Malignancies.International journal of molecular sciences · 2025Review
- Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.Cancer cell international · 2025Review
- Unveiling the potential of CLL-1: a promising target for AML therapy.Biomarker research · 2025Review
- T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma: Optimal Dosing Schedule and Duration of Treatment.Blood cancer discovery · 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
- IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells.Journal of hematology & oncology · 2024Article
- New immune cell engagers for cancer immunotherapy.Nature reviews. Immunology · 2024Review
- Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy.Acta pharmaceutica Sinica. B · 2024Review
- Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion.Biology · 2024Review
- Tuning the potency and selectivity of ImmTAC molecules by affinity modulation.Clinical and experimental immunology · 2024Article
- A bibliometric and knowledge-map analysis of bispecific antibodies in cancer immunotherapy from 2000 to 2023.Heliyon · 2024Article
- A CD3 humanized mouse model unmasked unique features of T-cell responses to bispecific antibody treatment.Blood advances · 2024Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a major unmet medical need. Most patients have poor long-term survival, and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacologic activity, pharmacokinetics, and safety of a CD3 T cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML. CLL-1 is prevalent in AML and, unlike other targets such as CD33 and CD123, is not expressed on hematopoietic stem cells providing potential hematopoietic recovery. We selected a high-affinity monkey cross-reactive anti-CLL-1 arm and tested several anti-CD3 arms that varied in affinity, and determined that the high-affinity CD3 arms were up to 100-fold more potent in vitro. However, in mouse models, the efficacy differences were less pronounced, probably because of prolonged exposure to TDB found with lower-affinity CD3 TDBs. In monkeys, assessment of safety and target cell depletion by the high- and low-affinity TDBs revealed that only the low-affinity CD3/CLL1 TDB was well tolerated and able to deplete target cells. Our data suggest that an appropriately engineered CLL-1 TDB could be effective in the treatment of AML.
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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.