ArticleJournal for immunotherapy of cancer2019
A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 78 citations in OpenAlex.
- PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Trial
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Fusion protein-mediated costimulation in engineered T cells: from intrinsic signaling to tumor microenvironment rewiring.Frontiers in immunology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- Advances in strategies to improve the immunotherapeutic efficacy of chimeric antigen receptor-T cell therapy for lymphoma.Cancer biology & medicine · 2025Review
- Chimeric switch and inverted cytokine receptors in T cell therapy: reprogramming T cells to overcome immune suppression in the solid tumor microenvironment.Frontiers in immunology · 2025Review
- Potentiating T cell tumor targeting using a combination of TCR with a Siglec-7 based CSR.Frontiers in immunology · 2025Article
- High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells.Nature communications · 2024Article
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies.International journal of molecular sciences · 2024Review
- Genetically engineering glycolysis in T cells increases their antitumor function.Journal for immunotherapy of cancer · 2024Article
- Immune Regulation and Immune Therapy in Melanoma: Review with Emphasis on CD155 Signalling.Cancers · 2024Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Targeting TIGIT for cancer immunotherapy: recent advances and future directions.Biomarker research · 2024Review
- Evolution of cell therapy for renal cell carcinoma.Molecular cancer · 2024Review
- Targeting TGFβ with chimeric switch receptor and secreted trap to improve T cells anti-tumor activity.Frontiers in immunology · 2024Article
- CAR-T Cell Therapy for Classical Hodgkin Lymphoma.HemaSphere · 2023Review
- Adoptive neoantigen-reactive T cell therapy: improvement strategies and current clinical researches.Biomarker research · 2023Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumors can employ different mechanisms to evade immune surveillance and function. Overexpression of co-inhibitory ligands that bind to checkpoint molecules on the surface of T-cells can greatly impair the function of latter. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is such a co-inhibitory receptor expressed by T and NK cells which, upon binding to its ligand (e.g., CD155), can diminish cytokine production and effector function. Additionally, the absence of positive co-stimulation at the tumor site can further dampen T-cell response.
methodsAs T-cell genetic engineering has become clinically-relevant in the recent years, we devised herein a strategy aimed at enhancing T-cell anti-tumor function by diverting T-cell coinhibitory signals into positive ones using a chimeric costimulatory switch receptor (CSR) composed of the TIGIT exodomain fused to the signaling domain of CD28.
resultsAfter selecting an optimized TIGIT-28 CSR, we co-transduced it along with tumor-specific TCR or CAR into human T-cells. TIGIT-28-equipped T-cells exhibited enhanced cytokine secretion and upregulation of activation markers upon co-culture with tumor cells. TIGIT-28 enhancing capability was also demonstrated in an original in vitro model of T-cell of hypofunction induction upon repetitive antigen exposure. Finally, we tested the function of this molecule in the context of a xenograft model of established human melanoma tumors and showed that TIGIT-28-engineered human T-cells demonstrated superior anti-tumor function.
conclusionOverall, we propose that TIGIT-based CSR can substantially enhance T-cell function and thus contribute to the improvement of engineered T cell-based immunotherapy.
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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.