ArticleOncology reports2021
Combining selective inhibitors of nuclear export (SINEs) with chimeric antigen receptor (CAR) T cells for CD19‑positive malignancies.
Article in Oncology reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape.ESMO open · 2026Review
- Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma.Cancer science · 2025Article
- Review
- Modulation of anti-tumour immunity by XPO1 inhibitors.Exploration of targeted anti-tumor therapy · 2025Review
- CRISPR-mediated generation of a tumor-associated antigen-deficient Raji platform to investigate antigen loss in CAR-T cell therapy.Frontiers in genome editing · 2025Article
- NEXUS: a phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies.Therapeutic advances in medical oncology · 2025Article
- [The mechanisms and salvage treatment strategies underlying positive relapse following CD19 CAR-T cell therapy in B-acute lymphoblastic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Review
- Exportin 1 governs the immunosuppressive functions of myeloid-derived suppressor cells in tumors through ERK1/2 nuclear export.Cellular & molecular immunology · 2024Article
- Treatment of multiple myeloma with selinexor: a review.Therapeutic advances in hematology · 2024Review
- A novel two-step administration of XPO-1 inhibitor may enhance the effect of anti-BCMA CAR-T in relapsed/refractory extramedullary multiple myeloma.Journal of translational medicine · 2023Article
- XPO1 inhibition sensitises CLL cells to NK cell mediated cytotoxicity and overcomes HLA-E expression.Leukemia · 2023Article
- Small-Molecule Compounds Boost CAR-T Cell Therapy in Hematological Malignancies.Current treatment options in oncology · 2023Review
- Impacting T-cell fitness in multiple myeloma: potential roles for selinexor and XPO1 inhibitors.Frontiers in immunology · 2023Review
- Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer.Vaccines · 2022Review
- CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges.Frontiers in immunology · 2022Review
- Therapeutic Targeting of Exportin-1 in Childhood Cancer.Cancers · 2021Review
- Selinexor Enhances NK Cell Activation Against Malignant B CellsFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cells directed against CD19 (CD19.CAR T cells) have yielded impressive clinical responses in the treatment of patients with lymphoid malignancies. However, resistance and/or relapse can limit treatment outcome. Risk of tumor escape can be reduced by combining treatment strategies. Selective inhibitors of nuclear export (SINEs) directed against nuclear exportin‑1 (XPO1) have demonstrated anti‑tumor efficacy in several hematological malignancies. The aim of the present study was to evaluate the combination of CAR T cells with the SINE compounds eltanexor and selinexor. As expected, eltanexor and selinexor were toxic to CD19‑positive malignant cells and the sensitivity of cells towards SINEs correlated with the levels of XPO1‑expression in ALL cell lines. When SINEs and CAR T cells were simultaneously combined, SINEs exerted toxicity towards CAR T cells and impaired their function affecting cytotoxicity and cytokine release ability. Flow cytometry and western blot analysis revealed that eltanexor decreased the cytoplasmic concentration of the transcription factor phosphorylated‑STAT3 in CAR T cells. Due to CAR T‑cell toxicity, sequential use of SINEs and CAR T cells was evaluated: Cytotoxicity of CAR T cells increased significantly when target cells were pre‑treated with the SINE compound eltanexor. In addition, exhaustion of CAR T cells decreased when target cells were pre‑treated with eltanexor. In summary, whereas the concomitant use of SINEs and CAR T cells does not seem advisable, sequential use of SINEs and CAR T cells might improve the anti‑tumor efficacy of CAR T cells.
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