ArticleJournal of neuro-oncology2019
Shortened ex vivo manufacturing time of EGFRvIII-specific chimeric antigen receptor (CAR) T cells reduces immune exhaustion and enhances antiglioma therapeutic function.
Article in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Label-free metabolic imaging monitors the fitness of chimeric antigen receptor T cells.Nature biomedical engineering · 2026Article
- Dynamic estimation of metabolic state during CAR T cell production.Cell reports methods · 2026Article
- Delivery platforms forFrontiers in immunology · 2026Review
- In vivo CAR-T cell engineering: concept, research progress, potential challenges and enhancement strategies.Experimental hematology & oncology · 2025Review
- Peptide-MHC-targeted retroviruses enable in vivo expansion and gene delivery to tumor-specific T cells.Science advances · 2025Article
- Advances in integrating biomaterials with CAR-T cells for enhancing solid tumor therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- In vivo CAR engineering for immunotherapy.Nature reviews. Immunology · 2025Review
- Strategies for Altering Delivery Technologies to Optimize CAR Therapy.International journal of molecular sciences · 2025Review
- Enhanced conversion of T cells into CAR T cells by modulation of the MAPK/ERK pathway.Cell reports. Medicine · 2025Article
- Comparative analysis and process optimization for manufacturing CAR-T using the PiggyBac system derived from cryopreserved versus fresh PBMCs.Scientific reports · 2025Article
- In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Intelligent Hydrogel-Assisted Hepatocellular Carcinoma Therapy.Research (Washington, D.C.) · 2024Review
- Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.Cancers · 2023Review
- Broadly neutralizing antibodies targeting HIV: Progress and challenges.Clinical immunology (Orlando, Fla.) · 2023Review
- Article
- Ganglioside-Functionalized Nanoparticles for Chimeric Antigen Receptor T-Cell Activation at the Immunological Synapse.ACS nano · 2022Article
- Precision medicine: In vivo CAR therapy as a showcase for receptor-targeted vector platforms.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer.Biomedicines · 2022Review
- Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors.Science advances · 2022Article
- Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-viral manufacturing of CAR T cells via the Sleeping Beauty transposon is cost effective and reduces the risk of insertional mutagenesis from viral transduction. However, the current gold standard methodology requires ex vivo numerical expansion of these cells on artificial antigen-presenting cells (AaPCs) for 4 weeks to generate CAR T cells of presumed sufficient quantity and function for clinical applications.
methodWe engineered EGFRvIII-specific CAR T cells and monitored phenotypic changes throughout their ex vivo manufacturing. To reduce the culture time required to generate the CAR T-cell population, we selected for T cells in peripheral blood mononuclear cells prior to CAR modification (to eliminate the competing NK cell population).
resultsWhile we found increased expression of exhaustion markers (such as PD-1, PD-L1, TIM-3, and LAG-3) after 2 weeks in culture, whose levels continued to rise over time, we were able to generate a CAR+ T-cell population with comparable CAR expression and cell numbers in 2 weeks, thereby reducing manufacturing time by 50%, with lower expression of immune exhaustion markers. The CAR T cells manufactured at 2 weeks showed superior therapeutic efficacy in mice bearing established orthotopic EGFRvIII+ U87 gliomas.
conclusionThese findings demonstrate a novel, rapid method to generate CAR T cells by non-viral modification that results in CAR T cells superior in phenotype and function and further emphasizes that careful monitoring of CAR T-cell phenotype prior to infusion is critical for generating an optimal CAR T-cell product with full antitumor potential.
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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.