ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Transforming growth factor-beta receptor blockade augments the effectiveness of adoptive T-cell therapy of established solid cancers.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
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- Emerging Novel Combined CAR-T Cell Therapies.Cancers · 2022Review
- DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation.Nature nanotechnology · 2021Article
- TGFβ biology in cancer progression and immunotherapy.Nature reviews. Clinical oncology · 2021Review
- Reprogramming Immune Cells for Enhanced Cancer Immunotherapy: Targets and Strategies.Frontiers in immunology · 2021Review
- Immune cell engineering: opportunities in lung cancer therapeutics.Drug delivery and translational research · 2020Review
- Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield.Cancers · 2020Review
- The application of nanotechnology in enhancing immunotherapy for cancer treatment: current effects and perspective.Nanoscale · 2019Review
- Blockade of TGF-β signaling to enhance the antitumor response is accompanied by dysregulation of the functional activity of CD4Journal of translational medicine · 2019Article
- Delivery technologies for cancer immunotherapy.Nature reviews. Drug discovery · 2019Review
- Current Progress in CAR-T Cell Therapy for Solid Tumors.International journal of biological sciences · 2019Review
- Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery.Nature biotechnology · 2018Article
- Naive CD4Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- CAR T Cell Therapy for Neuroblastoma.Frontiers in immunology · 2018Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAdoptive cellular immunotherapy is a promising approach to eradicate established tumors. However, a significant hurdle in the success of cellular immunotherapy involves recently identified mechanisms of immune suppression on cytotoxic T cells at the effector phase. Transforming growth factor-beta (TGF-beta) is one of the most important of these immunosuppressive factors because it affects both T-cell and macrophage functions. We thus hypothesized that systemic blockade of TGF-beta signaling combined with adoptive T-cell transfer would enhance the effectiveness of the therapy. EXPERIMENTAL
designFlank tumors were generated in mice using the chicken ovalbumin-expressing thymoma cell line, EG7. Splenocytes from transgenic OT-1 mice (whose CD8 T cells recognize an immunodominant peptide in chicken ovalbumin) were activated in vitro and adoptively transferred into mice bearing large tumors in the presence or absence of an orally available TGF-beta receptor-I kinase blocker (SM16).
resultsWe observed markedly smaller tumors in the group receiving the combination of SM16 chow and adoptive transfer. Additional investigation revealed that TGF-beta receptor blockade increased the persistence of adoptively transferred T cells in the spleen and lymph nodes, increased numbers of adoptively transferred T cells within tumors, increased activation of these infiltrating T cells, and altered the tumor microenvironment with a significant increase in tumor necrosis factor-alpha and decrease in arginase mRNA expression.
conclusionsWe found that systemic blockade of TGF-beta receptor activity augmented the antitumor activity of adoptively transferred T cells and may thus be a useful adjunct in future clinical trials.
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