ArticleHuman gene therapy methods2014
Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype.
Article in Human gene therapy methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
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- Inhibition of TBK1/IKKε mediated RIPK1 phosphorylation sensitizes tumors to immune cell killing.Cell death discovery · 2025Article
- Loss of ribosomal protein uL14 enables tumor escape from T cell immunosurveillance.NAR cancer · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
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- Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.Cancer cell · 2024Article
- Stem cell-derived CAR T cells show greater persistence, trafficking, and viral control compared to ex vivo transduced CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CD4Cellular & molecular immunology · 2024Article
- New insights into the stemness of adoptively transferred T cells by γc family cytokines.Cell communication and signaling : CCS · 2023Review
- Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function.Cell reports · 2023Article
- TSC2 regulates tumor susceptibility to TRAIL-mediated T-cell killing by orchestrating mTOR signaling.The EMBO journal · 2023Article
- An adverse tumor-protective effect of IDO1 inhibition.Cell reports. Medicine · 2023Article
- CD4Nature communications · 2023Article
- Innovative Strategies of Reprogramming Immune System Cells by Targeting CRISPR/Cas9-Based Genome-Editing Tools: A New Era of Cancer Management.International journal of nanomedicine · 2023Review
- MART-1 TCR gene-modified peripheral blood T cells for the treatment of metastatic melanoma: a phase I/IIa clinical trial.Immuno-oncology technology · 2022Article
- Combined analysis of T cell activation and T cell-mediated cytotoxicity by imaging cytometry.Journal of immunological methods · 2022Article
- RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells.Cell reports. Medicine · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advances in genetic engineering have made it possible to generate human T-cell products that carry desired functionalities, such as the ability to recognize cancer cells. The currently used strategies for the generation of gene-modified T-cell products lead to highly differentiated cells within the infusion product, and on the basis of data obtained in preclinical models, this is likely to impact the efficacy of these products. We set out to develop a good manufacturing practice (GMP) protocol that yields T-cell receptor (TCR) gene-modified T-cells with more favorable properties for clinical application. Here, we show the robust clinical-scale production of human peripheral blood T-cells with an early memory phenotype that express a MART-1-specific TCR. By combining selection and stimulation using anti-CD3/CD28 beads for retroviral transduction, followed by expansion in the presence of IL-7 and IL-15, production of a well-defined clinical-scale TCR gene-modified T-cell product could be achieved. A major fraction of the T-cells generated in this fashion were shown to coexpress CD62L and CD45RA, and express CD27 and CD28, indicating a central memory or memory stemlike phenotype. Furthermore, these cells produced IFNγ, TNFα, and IL-2 and displayed cytolytic activity against target cells expressing the relevant antigen. The T-cell products manufactured by this robust and validated GMP production process are now undergoing testing in a phase I/IIa clinical trial in HLA-A*02:01 MART-1-positive advanced stage melanoma patients. To our knowledge, this is the first clinical trial protocol in which the combination of IL-7 and IL-15 has been applied for the generation of gene-modified T-cell products.
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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.