ArticleBlood2021
Concomitant use of a dual Src/ABL kinase inhibitor eliminates the in vitro efficacy of blinatumomab against Ph+ ALL.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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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
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Efficacy and Safety of Immune Checkpoint Inhibitors in the Treatment of Hematologic Malignancies: An Umbrella Review of Systematic Reviews and Meta-Analyses.Cancer medicine · 2026Pooled it
- Efficacy and safety of chimeric antigen receptor T-cell in the treatment of hematologic malignancy: an umbrella review of systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Dynamics of in vivo immune remodeling in PhBlood cancer journal · 2026Article
- Interleukin signaling mitigates the inhibitory effects of combined Src/BCR-ABL1 blockade on T-cell activity in Philadelphia chromosome-positive acute lymphoblastic leukemia.Haematologica · 2026Article
- From the bench of molecular understanding to the bedside of optimal therapy forEJC paediatric oncology · 2025Article
- Review
- Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20Haematologica · 2024Article
- Combination Therapy With Asciminib and Ponatinib as a Bridge to Brexucabtagene Autoleucel and Maintenance in a Patient With Relapsed Refractory Philadelphia Positive B-Cell Acute Lymphoblastic Leukemia.Journal of medical cases · 2024Article
- Article
- Pathway of LCK Tyrosine Kinase and mTOR Signaling in Children with T-Cell Acute Lymphoblastic Leukemia.The application of clinical genetics · 2024Review
- PD-1 blockade in combination with dasatinib potentiates induction of anti-acute lymphocytic leukemia immunity.Journal for immunotherapy of cancer · 2023Article
- Differential inhibition of T-cell receptor and STAT5 signaling pathways determines the immunomodulatory effects of dasatinib in chronic phase chronic myeloid leukemia.Haematologica · 2023Article
- BCR::ABL1 tyrosine kinase inhibitors hamper the therapeutic efficacy of blinatumomab in vitro.Journal of cancer research and clinical oncology · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Ponatinib sensitizes myeloma cells to MEK inhibition in the high-risk VQ model.Scientific reports · 2022Article
- Novel strategies for the mitigation of cytokine release syndrome induced by T cell engaging therapies with a focus on the use of kinase inhibitors.Oncoimmunology · 2022Review
- JAK and mTOR inhibitors prevent cytokine release while retaining T cell bispecific antibody in vivo efficacy.Journal for immunotherapy of cancer · 2022Article
- Has Ph-like ALL Superseded Ph+ ALL as the Least Favorable Subtype?Best practice & research. Clinical haematology · 2021Review
- Novel Treatment Strategies Utilizing Immune Reactions against Chronic Myelogenous Leukemia Stem Cells.Cancers · 2021Review
- Src/lck inhibitor dasatinib reversibly switches off cytokine release and T cell cytotoxicity following stimulation with T cell bispecific antibodies.Journal for immunotherapy of cancer · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Blinatumomab is currently approved for use as a single agent in relapsed and refractory acute lymphoblastic leukemia (ALL). Cytotoxicity is mediated via signaling through the T-cell receptor (TCR). There is now much interest in combining blinatumomab with targeted therapies, particularly in Philadelphia chromosome-positive ALL (Ph+ ALL). However, some second- and third-generation ABL inhibitors also potently inhibit Src family kinases that are important in TCR signaling. We combined ABL inhibitors and dual Src/ABL inhibitors with blinatumomab in vitro from both healthy donor samples and primary samples from patients with Ph+ ALL. Blinatumomab alone led to both T-cell proliferation and elimination of target CD19+ cells and enhanced production of interferon-γ (IFN-γ). The addition of the ABL inhibitors imatinib or nilotinib to blinatumomab did not inhibit T-cell proliferation or IFN-γ production. However, the addition of dasatinib or ponatinib inhibited T-cell proliferation and IFN-γ production. Importantly, there was no loss of CD19+ cells treated with blinatumomab plus dasatinib or ponatinib in healthy samples or samples with a resistant ABL T315I mutation by dasatinib in combination with blinatumomab. These in vitro findings bring pause to the excitement of combination therapies, highlighting the importance of maintaining T-cell function with targeted therapies.
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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.