ArticleCancer science2021
Inhibition of MEK pathway enhances the antitumor efficacy of chimeric antigen receptor T cells against neuroblastoma.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis 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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Low blood level of tumour suppressor miR-5193 as a target of immunotherapy to PD-L1 in gastric cancer.British journal of cancer · 2024Pooled it
- Redifferentiation-enabled TSHRCART cells overcome antigen loss in aggressive thyroid cancers.Molecular cancer · 2026Article
- Alectinib boosts anti-tumor efficacy of disialoganglioside 2 chimeric antigen receptor T cells in ALK-mutated neuroblastoma by suppressing programmed death-ligand 1.British journal of cancer · 2026Article
- Reprogramming the tumor microenvironment via TFF3 targeting: a potential novel avenue to boost CAR-T cell therapy in solid tumors.Cancer gene therapy · 2026Review
- Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia.Nature communications · 2025Article
- Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Expression Profiles of Five Common Cancer Membrane Protein Antigens Collected for the Development of Cocktail CAR-T Cell Therapies Applicable to Most Solid Cancer Patients.International journal of molecular sciences · 2025Article
- Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.Cancer immunology, immunotherapy : CII · 2025Article
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB.Signal transduction and targeted therapy · 2024Article
- Preclinical evidence for employing MEK inhibition in NRAS mutated pediatric gastroenteropancreatic neuroendocrine-like tumors.Translational oncology · 2024Article
- Manipulating the tumor immune microenvironment to improve cancer immunotherapy: IGF1R, a promising target.Frontiers in immunology · 2024Review
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Adoptive cell therapy in paediatric extracranial solid tumours: current approaches and future challenges.European journal of cancer (Oxford, England : 1990) · 2023Review
- piggyBac-transposon-mediated CAR-T cells for the treatment of hematological and solid malignancies.International journal of clinical oncology · 2023Review
- Genetic dysregulation of immunologic and oncogenic signaling pathways associated with tumor-intrinsic immune resistance: a molecular basis for combination targeted therapy-immunotherapy for cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Enhancing GD2 CAR T-cell therapy with IGF-1R blockade: Are DIPG CAR T cells ready for combinatorial therapy?Neuro-oncology · 2022Article
- The Past, Present, and Future of Non-Viral CAR T Cells.Frontiers in immunology · 2022Review
- Inhibition of MEK pathway enhances the antitumor efficacy of chimeric antigen receptor T cells against neuroblastoma.Cancer science · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Disialoganglioside (GD2)-specific chimeric antigen receptor (CAR)-T cells (GD2-CAR-T cells) have been developed and tested in early clinical trials in patients with relapsed/refractory neuroblastoma. However, the effectiveness of immunotherapy using these cells is limited, and requires improvement. Combined therapy with CAR-T cells and molecular targeted drugs could be a promising strategy to enhance the antitumor efficacy of CAR T cell immunotherapy. Here, we generated GD2-CAR-T cells through piggyBac transposon (PB)-based gene transfer (PB-GD2-CAR-T cells), and analyzed the combined effect of these cells and a MEK inhibitor in vitro and in vivo on neuroblastoma. Trametinib, a MEK inhibitor, ameliorated the killing efficacy of PB-GD2-CAR-T cells in vitro, whereas a combined treatment of the two showed superior antitumor efficacy in a murine xenograft model compared to that of PB-GD2-CAR-T cell monotherapy, regardless of the mutation status of the MAPK pathway in tumor cells. The results presented here provide new insights into the feasibility of combined treatment with CAR-T cells and MEK inhibitors in patients with neuroblastoma.
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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.