ArticleCancer research2011
Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 123 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
123 citing papers in PubMed, 197 citations in OpenAlex.
- Epigenetic regulation of T cell exhaustion in cancer.Nature reviews. Cancer · 2026Review
- Resistance mechanisms and overcoming strategies for CAR T-cell therapy in B-cell hematologic malignancies.Frontiers in immunology · 2026Review
- Impact of IL-21 on CAR T-cell manufacturing: phenotypic, metabolic, and functional outcomes.Frontiers in immunology · 2026Article
- CAR NK cell production from human cord blood NK progenitor cells is enhanced by stimulation of the IL-15 receptor.Cancer immunology, immunotherapy : CII · 2025Article
- CAR-T cell therapy for cancer: current challenges and future directions.Signal transduction and targeted therapy · 2025Review
- Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- CAR T Cell Nanosymbionts: Revealing the Boundless Potential of a New Dyad.International journal of molecular sciences · 2024Review
- Advancing Chimeric Antigen Receptor T-Cell Therapy for Acute Myeloid Leukemia: Current Limitations and Emerging Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- [Modification with IL-21 and CCL19 enhances killing efficiency and tumor infiltration of NKP30 CAR-T cells in lung cancer].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- A Customizable Platform to Integrate CAR and Conditional Expression of Immunotherapeutics in T Cells.International journal of molecular sciences · 2024Article
- Targeting epigenetic regulation and post-translational modification with 5-Aza-2' deoxycytidine and SUMO E1 inhibition augments T-cell receptor therapy.Journal for immunotherapy of cancer · 2024Article
- Artificial antigen-presenting cells: the booster for the obtaining of functional adoptive cells.Cellular and molecular life sciences : CMLS · 2024Review
- Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling.Nature cancer · 2024Article
- Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8Nature communications · 2024Article
- A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- Car T Cells in Solid Tumors: Overcoming Obstacles.International journal of molecular sciences · 2024Review
- Article
- Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function.Cancer immunology research · 2023Article
- Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer.Archivum immunologiae et therapiae experimentalis · 2023Review
- Strategies for Reducing Toxicity and Enhancing Efficacy of Chimeric Antigen Receptor T Cell Therapy in Hematological Malignancies.International journal of molecular sciences · 2023Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Improving the therapeutic efficacy of T cells expressing a chimeric antigen receptor (CAR) represents an important goal in efforts to control B-cell malignancies. Recently an intrinsic strategy has been developed to modify the CAR itself to improve T-cell signaling. Here we report a second extrinsic approach based on altering the culture milieu to numerically expand CAR(+) T cells with a desired phenotype, for the addition of interleukin (IL)-21 to tissue culture improves CAR-dependent T-cell effector functions. We used electrotransfer of Sleeping Beauty system to introduce a CAR transposon and selectively propagate CAR(+) T cells on CD19(+) artificial antigen-presenting cells (aAPC). When IL-21 was present, there was preferential numeric expansion of CD19-specific T cells which lysed and produced IFN-γ in response to CD19. Populations of these numerically expanded CAR(+) T cells displayed an early memory surface phenotype characterized as CD62L(+)CD28(+) and a transcriptional profile of naïve T cells. In contrast, T cells propagated with only exogenous IL-2 tended to result in an overgrowth of CD19-specific CD4(+) T cells. Furthermore, adoptive transfer of CAR(+) T cells cultured with IL-21 exhibited improved control of CD19(+) B-cell malignancy in mice. To provide coordinated signaling to propagate CAR(+) T cells, we developed a novel mutein of IL-21 bound to the cell surface of aAPC that replaced the need for soluble IL-21. Our findings show that IL-21 can provide an extrinsic reprogramming signal to generate desired CAR(+) T cells for effective immunotherapy.
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What OpenQuestion holds
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.