ArticleLeukemia2016
Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 245 citations in OpenAlex.
- Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma.Blood · 2025Trial
- Association of HLA class I type with prevalence and outcome of patients with acute myeloid leukemia and mutated nucleophosmin.PloS one · 2018Trial
- Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia.Oncotarget · 2016Trial
- Research Progress and Optimization Strategies of Bispecific Antibody Therapies for CLDN18.2-Positive Gastric Cancer.Journal of gastrointestinal cancer · 2026Review
- Efficient in vivo assembly of DNA encoded polyvalent BTEs for dual antigen targeting for broadening therapeutic impact in ovarian cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Effector-to-target ratio as a translational bottleneck for CD33 T-cell engagers in acute myeloid leukemia: a quantitative reanalysis of AMG 330.Investigational new drugs · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The safety and efficacy of bispecific T-cell engagers (TCEs) in patients with glioma.Clinical and experimental medicine · 2026Review
- Pre-therapeutic bone marrow-resident leukemic cells in acute myeloid leukemia exhibit a distinct dysregulated calcium signature and stem-like profile reflecting minimal residual disease precursors.Journal of experimental & clinical cancer research : CR · 2026Article
- Overcoming resistance to immune checkpoint inhibitor therapy in acute myeloid leukemia.Frontiers in oncology · 2026Review
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.Frontiers in immunology · 2026Review
- CD123-targeting immunotherapeutic approaches in acute myeloid leukaemia.British journal of haematology · 2025Review
- Clinical development of immuno-oncology therapeutics.Cancer letters · 2025Review
- The rewired immune microenvironment in leukemia.Nature immunology · 2025Review
- The high-risk model associated with SYTL4 predicts poor prognosis and correlates with immune infiltration in AML.Biochemistry and biophysics reports · 2025Article
- Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment.Antibodies (Basel, Switzerland) · 2025Review
- Incorporating mRNA therapeutics into biological treatments of hematologic malignancies.Frontiers in immunology · 2025Review
- Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.International journal of biological sciences · 2025Review
- Advances in cancer immunotherapy: Strategies and innovations strategies for adoptive immunotherapy of cancer.Iranian journal of basic medical sciences · 2025Review
95 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bispecific T-cell engagers (BiTEs) are very effective in recruiting and activating T cells. We tested the cytotoxicity of the CD33/CD3 BiTE antibody construct AMG 330 on primary acute myeloid leukemia (AML) cells ex vivo and characterized parameters contributing to antileukemic cytolytic activity. The E:T ratio and the CD33 expression level significantly influenced lysis kinetics in long-term cultures of primary AML cells (n=38). AMG 330 induced T-cell-mediated proinflammatory conditions, favoring the upregulation of immune checkpoints on target and effector cells. Although not constitutively expressed at the time of primary diagnosis (n=123), PD-L1 was strongly upregulated on primary AML cells upon AMG 330 addition to ex vivo cultures (n=27, P<0.0001). This phenomenon was cytokine-driven as the sole addition of interferon (IFN)-γ and tumor necrosis factor-α also induced expression. Through blockade of the PD-1/PD-L1 interaction, AMG 330-mediated lysis (n=9, P=0.03), T-cell proliferation (n=9, P=0.01) and IFN-γ secretion (n=8, P=0.008) were significantly enhanced. The combinatorial approach was most beneficial in settings of protracted AML cell lysis. Taken together, we have characterized a critical resistance mechanism employed by primary AML cells under AMG 330-mediated proinflammatory conditions. Our results support the evaluation of checkpoint molecules in upcoming clinical trials with AMG 330 to enhance BiTE antibody construct-mediated cytotoxicity.
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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.