ArticleJournal of cancer research and clinical oncology2022
BCR::ABL1 tyrosine kinase inhibitors hamper the therapeutic efficacy of blinatumomab in vitro.
Article in Journal of cancer research and clinical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- Short-term blinatumomab for B-cell acute lymphoblastic leukemia pediatric patients results in measurable residual disease clearance.Annals of hematology · 2026Trial
- 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
- 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
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAcute B-lymphoblastic leukemia (B-ALL) is a malignant disease characterized by accumulation of clonal immature lymphocytes in the bone marrow and peripheral blood. The approval of BCR::ABL1 tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib and ponatinib marked a milestone in targeted therapy only for a subset of patients carrying the translocation t(9;22)(q34;q11). Immunotherapy with the bispecific antibody (bsAb) blinatumomab targeting CD19xCD3 revolutionized treatment of all B-ALL cases. The combination of both TKI and bsAb, so-called "dual targeting", is currently under clinical investigation, although TKI might influence T cell effects.
methodsWe here investigated the combination of different TKI and blinatumomab in BCR::ABL1
resultsIn vitro analysis revealed profound reduction of T cell proliferation, differentiation, cytokine release and killing of tumor cells upon application of BCR::ABL1 TKI with blinatumomab. Inhibition was more pronounced with dasatinib and ponatinib compared to nilotinib and imatinib. T cell signalling after CD3 stimulation was impaired by TKI mirrored by inhibition of LCK phosphorylation. This known off-target effect might influence the efficacy of bsAb therapy when combined with BCR::ABL1 TKI.
conclusionIn conclusion, we propose that nilotinib and imatinib might also be suitable substances for combination with blinatumomab and suggest evaluation in clinical trials.
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