ArticleCytotherapy2014
Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.
Article in Cytotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B-cell acute lymphoblastic leukemia with high-risk features.Blood advances · 2020Trial
- Toward a chemotherapy and allo-HSCT free future: the evolution of treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia.Frontiers in immunology · 2026Review
- Good manufacturing practice-grade generation of CD19 and CD123-specific CAR-T cells using piggyBac transposon and allogeneic feeder cells in patients diagnosed with B-cell non-Hodgkin lymphoma and acute myeloid leukemia.Frontiers in immunology · 2024Article
- Current status of CAR-T cell therapy for pediatric hematologic malignancies.International journal of clinical oncology · 2023Review
- piggyBac-transposon-mediated CAR-T cells for the treatment of hematological and solid malignancies.International journal of clinical oncology · 2023Review
- A Brief Introduction to Current Cancer Gene Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VII. Present and future of technologies for production of CAR cell therapies.Hematology, transfusion and cell therapy · 2021Article
- Article
- Autologous antigen-presenting cells efficiently expandMolecular therapy. Methods & clinical development · 2021Article
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- αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib.Journal for immunotherapy of cancer · 2021Article
- Mutated GM-CSF-based CAR-T cells targeting CD116/CD131 complexes exhibit enhanced anti-tumor effects against acute myeloid leukaemia.Clinical & translational immunology · 2021Article
- Evaluation of NonviralFrontiers in immunology · 2021Article
- Clinical Utility of Droplet Digital PCR to Monitor BCR-ABL1 Transcripts of Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Post-chimeric Antigen Receptor19/22 T-Cell Cocktail Therapy.Frontiers in oncology · 2021Article
- CAR T-Cell Production Using Nonviral Approaches.Journal of immunology research · 2021Review
- Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies.International journal of molecular sciences · 2020Review
- Direct Delivery ofMolecular therapy oncolytics · 2020Article
- CAR T Cell Generation byMolecular therapy. Methods & clinical development · 2020Article
- Genome Engineering Renal Epithelial Cells for Enhanced Volume Transport Function.Cellular and molecular bioengineering · 2020Article
- Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
Abstract
BACKGROUND
aimsTo develop a treatment option for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant to tyrosine kinase inhibitors (TKIs), we evaluated the anti-leukemic activity of T cells non-virally engineered to express a CD19-specific chimeric antigen receptor (CAR).
methodsA CD19.CAR gene was delivered into mononuclear cells from 10 mL of blood of healthy donors through the use of piggyBac-transposons and the 4-D Nucleofector System. Nucleofected cells were stimulated with CD3/CD28 antibodies, magnetically selected for the CD19.CAR, and cultured in interleukin-15-containing serum-free medium with autologous feeder cells for 21 days. To evaluate their cytotoxic potency, we co-cultured CAR T cells with seven Ph(+)ALL cell lines including three TKI-resistant (T315I-mutated) lines at an effector-to-target ratio of 1:5 or lower without cytokines.
resultsWe obtained ∼1.3 × 10(8) CAR T cells (CD4(+), 25.4%; CD8(+), 71.3%), co-expressing CD45RA and CCR7 up to ∼80%. After 7-day co-culture, CAR T cells eradicated all tumor cells at the 1:5 and 1:10 ratios and substantially reduced tumor cell numbers at the 1:50 ratio. Kinetic analysis revealed up to 37-fold proliferation of CAR T cells during a 20-day culture period in the presence of tumor cells. On exposure to tumor cells, CAR T cells transiently and reproducibly upregulated the expression of transgene as well as tumor necrosis factor-related apoptosis-inducing ligand and interleukin-2.
conclusionsWe generated a clinically relevant number of CAR T cells from 10 mL of blood through the use of piggyBac-transposons, a 4D-Nulcleofector, and serum/xeno/tumor cell/virus-free culture system. CAR T cells exhibited marked cytotoxicity against Ph(+)ALL regardless of T315I mutation. PiggyBac-mediated CD19-specific T-cell therapy may provide an effective, inexpensive and safe option for drug-resistant Ph(+)ALL.
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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.