ArticleFrontiers in immunology2024
Optimized BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21 robustly control multiple myeloma.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Affinity and costimulatory architecture-associated toxicity in mesothelin-targeted TCR-mimetic CAR-T cells.Frontiers in immunology · 2026Article
- CXCR3 enhanced murine chimeric antigen receptor T cells in the treatment of solid tumors.Translational cancer research · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
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11 authors.
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Abstract
Introduction: Challenges remain in reducing antigen escape and tumor recurrence while CAR-T cell therapy has substantially improved outcomes in the treatment of multiple myeloma. T cell receptor fusion construct (TRuC)-T cells, which utilize intact T cell receptor (TCR)-CD3 complex to eliminate tumor cells in a non-major histocompatibility complex (MHC)-restricted manner, represent a promising strategy. Moreover, interleukin-7 (IL-7) is known to enhance the proliferation and survival of T cells. C-C motif chemokine ligand 21 (CCL21) is a ligand for chemokine C-C motif receptor 7 (CCR7) and exhibits strong chemotaxis against naïve T cells and antigen-presenting cells such as dendritic cells. Methods: The bispecific TRuC-T cells simultaneously targeting B cell maturation antigen (BCMA) and CD2 subset 1 (CS1) were constructed by pairing two of five subunits (i.e., TCRαC, TCRβC, CD3γ, CD3δ, and CD3ϵ) in the TCR/CD3 complex and were named C-AC-B-3E, C-BC-B-3E, C-3G-B-3E, C-3D-B-3E, C-3E-B-3E, B-3E-C-3E, B-3G-C-3E, and B-3D-C-3E. Additionally, the BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21, named BC-7×21 TRuC-T cells, were generated. All of the bispecific TRuC-T cells were characterized and tested Results: Following the optimization of various pairs of two subunits of TCR/CD3 complex, B-3G-C-3E TRuC-T cells, characterized by incorporating CD3γ and CD3ε, exhibited the strongest myeloma-specific cytotoxicity. Furthermore, the bispecific BC-7×21 TRuC-T cells had stronger proliferation, chemotaxis, and cytotoxicity Discussion: This study demonstrated that BC-7×21 TRuC-T cells, engineered through the optimization of the two subunits of TCR/CD3 complex and a co-expression cytokine strategy, may offer a novel and effective therapy for relapsed/refractory multiple myeloma.
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