ArticleJournal for immunotherapy of cancer2020
Cell-based artificial APC resistant to lentiviral transduction for efficient generation of CAR-T cells from various cell sources.
Article in Journal for immunotherapy of cancer, 2020. 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, 27 citations in OpenAlex.
- Engineered artificial antigen-presenting cells for tumor immunotherapy: Design strategies, clinical applications, and translational challenges.Materials today. Bio · 2026Review
- Chemistry-mediated synthetic virus-cell interaction as a generic approach to enhance gene delivery to mammalian cells.Molecular therapy. Advances · 2026Article
- Current Developments of CAR-T and CAR-NK Cell Therapies for Ovarian Cancer.Stem cell reviews and reports · 2026Review
- CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.Current gene therapy · 2026Review
- Breakthrough for Anticancer Immunotherapy: Current Advances in Manufacturing Protocols of Chimeric Antigen Receptor-Based Therapies.Antibodies (Basel, Switzerland) · 2025Review
- Artificial antigen-presenting cells: the booster for the obtaining of functional adoptive cells.Cellular and molecular life sciences : CMLS · 2024Review
- Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation.Annals of laboratory medicine · 2024Review
- Article
- Chemical genetic control of cytokine signaling in CAR-T cells using lenalidomide-controlled membrane-bound degradable IL-7.Leukemia · 2024Article
- CRISPR-Cas9 in basic and translational aspects of cancer therapy.BioImpacts : BI · 2024Review
- Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy.Frontiers in molecular medicine · 2024Review
- Characterization of CAR T Cells Manufactured Using Genetically Engineered Artificial Antigen Presenting Cells.Cell journal · 2023Article
- Synthetic Antigen-Presenting Cells for Adoptive T Cell Therapy.Advanced therapeutics · 2021Article
- A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies.Stem cell research & therapy · 2021Review
- Combination of CRISPR/Cas9 System and CAR-T Cell Therapy: A New Era for Refractory and Relapsed Hematological Malignancies.Current medical science · 2021Review
- Myeloid Immune Cells CARrying a New Weapon Against Cancer.Frontiers in cell and developmental biology · 2021Review
- Antigen-Presenting Cells: Potential of Proven und New Players in Immune Therapies.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2020Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAdoptive cell therapy with chimeric antigen receptor T cells (CAR-T) has become a standard treatment for patients with certain aggressive B cell malignancies and holds promise to improve the care of patients suffering from numerous other cancers in the future. However, the high manufacturing cost of CAR-T cell therapies poses a major barrier to their broader clinical application. Among the key cost drivers of CAR-T production are single-use reagents for T cell activation and clinical-grade viral vector. The presence of variable amounts of contaminating monocytes in the starting material poses an additional challenge to CAR-T manufacturing, since they can impede T cell stimulation and transduction, resulting in manufacturing failure.
methodsWe created K562-based artificial antigen-presenting cells (aAPC) with genetically encoded T cell stimulation and costimulation that represent an inexhaustible source for T cell activation. We additionally disrupted endogenous expression of the low-density lipoprotein receptor (LDLR) on these aAPC (aAPC-ΔLDLR) using CRISPR-Cas9 gene editing nucleases to prevent inadvertent lentiviral transduction and avoid the sink effect on viral vector during transduction. Using various T cell sources, we produced CD19-directed CAR-T cells via aAPC-ΔLDLR-based activation and tested their in vitro and in vivo antitumor potency against B cell malignancies.
resultsWe found that lack of LDLR expression on our aAPC-ΔLDLR conferred resistance to lentiviral transduction during CAR-T production. Using aAPC-ΔLDLR, we achieved efficient expansion of CAR-T cells even from unpurified starting material like peripheral blood mononuclear cells or unmanipulated leukapheresis product, containing substantial proportions of monocytes. CD19-directed CAR-T cells that we produced via aAPC-ΔLDLR-based expansion demonstrated potent antitumor responses in preclinical models of acute lymphoblastic leukemia and B-cell lymphoma.
conclusionsOur aAPC-ΔLDLR represent an attractive approach for manufacturing of lentivirally transduced T cells that may be simpler and more cost efficient than currently available methods.
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