ArticleJournal of hematology & oncology2018
Anti-GD2/4-1BB chimeric antigen receptor T cell therapy for the treatment of Chinese melanoma patients.
Article in Journal of hematology & oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 186 citations in OpenAlex.
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- Review
- Immunotherapy in melanoma: advances, pitfalls, and future perspectives.Frontiers in molecular biosciences · 2024Review
- Prostate Cancer Organoids for Tumor Modeling and Drug Screening.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Multidisciplinary approach and treatment of acral and mucosal melanoma.Frontiers in oncology · 2024Review
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- Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score.Cell death discovery · 2023Article
- Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy.Cancers · 2023Review
- Pathology and Molecular Biology of Melanoma.Current issues in molecular biology · 2023Review
- Bispecific antibodies redirect synthetic agonistic receptor modified T cells against melanoma.Journal for immunotherapy of cancer · 2023Article
- Patient-derived xenograft models in cancer therapy: technologies and applications.Signal transduction and targeted therapy · 2023Review
- The biological role and immunotherapy of gangliosides and GD3 synthase in cancers.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression of ganglioside GD2 in non-Caucasian melanoma populations for the first time, thus providing a basis for future clinical research.
methodsThis study included tumor samples from 288 melanoma patients at the Peking University Cancer Hospital & Institute. Clinical data were collected. Immunohistochemical assays using antibodies against ganglioside GD2 were performed on formalin-fixed, paraffin-embedded specimens. The ability of ganglioside GD2 CAR-T cells to kill ganglioside GD2
resultsAmong the 288 samples, 49.3% of cases (142/288) demonstrated positive staining with ganglioside GD2. The median survival time in patients exhibiting ganglioside GD2 expression was significantly shorter than that in patients without ganglioside GD2 expression (31 vs. 47.1 months, P < 0.001). In the present study, CAR was constructed using a GD2-specific scFv (14.G2a), T cell receptor CD3ζ chain, and the CD137 (4-1BB) costimulatory motif. In addition, the GD2.BBζ CAR-T cells demonstrated specific lysis of ganglioside GD2-expressing melanoma cells in vitro. In two PDX models, mice that received intravenous or local intratumor injections of GD2.BBζ CAR-T cells experienced rapid tumor regression.
conclusionsThese data demonstrate that the rate of GD2 expression in Chinese patients is 49.3%. GD2.BBζ CAR-T cells can both efficiently lyse melanoma in a GD2-specific manner and release Th1 cytokines in an antigen-dependent manner in vitro and in vivo. Anti-GD2/4-1BB CAR-T cells represent a clinically appealing treatment strategy for Chinese melanoma patients exhibiting GD2 expression and provide a basis for future studies of the clinical application of immunotherapy for melanoma.
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