ArticleLeukemia2021
IL-6 trans-signaling promotes the expansion and anti-tumor activity of CAR T cells.
Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
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Who cites it
38 citing papers in PubMed, 48 citations in OpenAlex.
- Distinct patient, tumour and chimeric antigen receptor T-cell characteristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed and refractory multiple myeloma.British journal of haematology · 2025Trial
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Lung tumouroids as a testing platform for precision CAR T cell therapy.Nature biomedical engineering · 2026Article
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- Interleukin 6 Drives Durable T Cell-Mediated Immunity to Pancreatic Cancer.Cellular and molecular gastroenterology and hepatology · 2026Article
- Interleukin-6, CD8Frontiers in aging neuroscience · 2026Review
- Article
- Interleukin 6 drives durable T cell-mediated immunity to pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- Emerging Strategies of Cell and Gene Therapy Targeting Tumor Immune Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Chimeric Antigen Receptor-T Cells in the Modern Era of Chronic Lymphocytic Leukemia Treatment.Cancers · 2025Review
- Immunomodulatory effects of intratumoral cowpea mosaic virus and calreticulin nanoparticles in canine tumors: early results.Frontiers in immunology · 2025Article
- Targeting the Exon2 splice cis-element in PD-1 and its effects on lymphocyte function.PloS one · 2025Article
- Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.HemaSphere · 2024Article
- Emerging Therapeutic Targets and Drug Resistance Mechanisms in Immunotherapy of Hematological Malignancies.Cancers · 2023Review
- CAR designs for solid tumors: overcoming hurdles and paving the way for effective immunotherapy.Biophysics reports · 2023Article
- Strategies for Reducing Toxicity and Enhancing Efficacy of Chimeric Antigen Receptor T Cell Therapy in Hematological Malignancies.International journal of molecular sciences · 2023Review
- [Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
Corrections and comments
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Authors and funding
29 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cell therapies lead to high clinical response rates in B cell malignancies, and are under investigation for treatment of solid tumors. While high systemic interleukin- (IL-) 6 levels are associated with clinical cytokine release syndrome (CRS), the role of IL-6 trans-signaling within CAR T-cells has not been reported. We generated CAR T cells that constitutively express hyper IL-6 (HIL-6), a designer cytokine that activates the trans-signaling pathway. HIL-6-expressing CAR T-cells exhibited enhanced proliferation and antitumor efficacy in vitro and in xenograft models. However, HIL-6 CAR T cells caused severe graft-versus-host disease (GVHD). Transcriptomic profiling revealed that HIL-6 stimulation of CAR T cells upregulated genes associated with T cell migration, early memory differentiation, and IL-6/GP130/STAT3 signaling. Since IL-6 trans-signaling acts via surface GP130, we generated CAR T cells expressing a constitutively-active form of GP130 and found these retained improved antitumor activity without signs of GVHD in preclinical models of B-cell leukemia and solid tumors. Taken together, these results show that IL-6 trans-signaling can enhance expansion and antitumor activity of CAR T cells via the GP130/STAT3 pathway, and suggest that expression of GP130 within CAR T cells could lead to improved antitumor efficacy without systemic IL-6 trans-signaling.
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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.