ArticleCell death & disease2019
T-cell receptor gene therapy targeting melanoma-associated antigen-A4 by silencing of endogenous TCR inhibits tumor growth in mice and human.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Therapeutic Vulnerabilities of the Key Genetic Drivers in Leiomyosarcoma.Medical sciences (Basel, Switzerland) · 2026Review
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Immunotherapy for Leiomyosarcoma: Current Status and Perspectives.Journal of immunology research · 2026Review
- T-Cell Responses and T-Cell-Based Therapy in Acute Myeloid Leukemia.Current medical science · 2025Review
- Melanoma-associated antigen A4: A cancer/testis antigen as a target for adoptive T-cell receptor T-cell therapy.Cancer treatment reviews · 2025Review
- Targeting cancer with precision: strategical insights into TCR-engineered T cell therapies.Theranostics · 2025Review
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- Review
- T-Cell Receptor Mimic Antibodies for Cancer Immunotherapy.Molecular cancer therapeutics · 2021Review
- Overview of Cellular Immunotherapies within Transfusion Medicine for the Treatment of Malignant Diseases.International journal of molecular sciences · 2021Review
- Emerging roles of the MAGE protein family in stress response pathways.The Journal of biological chemistry · 2020Review
- Chimeric Antigen Receptor Therapy: How Are We Driving in Solid Tumors?Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020Review
- Review
- Adoptive T cell therapy: Boosting the immune system to fight cancer.Seminars in immunology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetically engineered T cells expressing a T-cell receptor (TCR) are powerful tools for cancer treatment and have shown significant clinical effects in sarcoma patients. However, mismatch of the introduced TCR α/β chains with endogenous TCR may impair the expression of transduced TCR, resulting in an insufficient antitumor capacity of modified T cells. Here, we report the development of immunotherapy using human lymphocytes transduced with a codon-optimized melanoma-associated antigen (MAGE)-A4 and HLA-A*2402-restricted TCR, which specifically downregulate endogenous TCR by small interfering RNA (si-TCR). We evaluated the efficacy of this immunotherapy in both NOD-SCID mice and uterine leiomyosarcoma patients. Our results revealed that transduced human lymphocytes exhibited high surface expression of the introduced tumor-specific TCR, enhanced cytotoxic activity against antigen-expressing tumor cells, and increased interferon-γ production by specific MAGE-A4 peptide stimulation. Retarded tumor growth was also observed in NOD-SCID mice inoculated with human tumor cell lines expressing both MAGE-A4 and HLA-A*2402. Furthermore, we report the successful management of a case of uterine leiomyosarcoma treated with MAGE-A4 si-TCR/HLA-A*2402 gene-modified T cells. Our results indicate that the TCR-modified T cell therapy is a promising novel strategy for cancer treatment.
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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.