ArticleJournal for immunotherapy of cancer2023
Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into the
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.Experimental hematology & oncology · 2026Review
- Affinity and costimulatory architecture-associated toxicity in mesothelin-targeted TCR-mimetic CAR-T cells.Frontiers in immunology · 2026Article
- Chimeric CD3ζ chains containing CD28 signalling motifs enhance antigen-specific IL-2 production and expansion of human TCR-engineered T cellsImmunotherapy advances · 2026Article
- CRISPR-Cas9 in leukemia immunotherapy: precision engineering of CAR-T cells and tumor-microenvironment modulation.Molecular biology reports · 2025Review
- Single-stranded HDR templates with truncated Cas12a-binding sequences improve knock-in efficiencies in primary human T cells.Molecular therapy. Nucleic acids · 2025Article
- Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis.Science advances · 2025Article
- ITM2A as a potential prognostic marker for triple-negative breast cancer.Journal of Cancer · 2025Article
- Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway.Journal of pharmaceutical analysis · 2024Article
- The recent advancement of TCR-T cell therapies for cancer treatment.Acta biochimica et biophysica Sinica · 2024Review
- Synthetic Cells and Molecules in Cellular Immunotherapy.International journal of biological sciences · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe incorporation of co-stimulatory signaling domains into second-generation chimeric antigen receptors (CARs) significantly enhances the proliferation and persistence of CAR-T cells in vivo, leading to successful clinical outcomes.
methodsTo achieve such functional enhancement in transgenic T-cell receptor-engineered T-cell (TCR-T) therapy, we designed a second-generation TCR-T cell in which CD3ζ genes modified to contain the intracellular domain (ICD) of the 4-1BB receptor were selectively inserted into the
resultsThis modification enabled the simultaneous recruitment of key adaptor molecules for signals 1 and 2 on TCR engagement. However, the addition of full-length 4-1BB ICD unexpectedly impaired the expression and signaling of TCRs, leading to suboptimal antitumor activity of the resulting TCR-T cells in vivo. We found that the basic-rich motif (BRM) in the 4-1BB ICD was responsible for the undesirable outcomes, and that fusion of minimal tumor necrosis factor receptor-associated factor (TRAF)-binding motifs at the C-terminus of CD3ζ (zBB
conclusionsOur findings offer a promising strategy for improving the intracellular signaling of TCR-T cells and their application in treating solid tumors.
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