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As a leading cell therapeutics provider, Creative Biolabs focuses on the genetic engineering of T cells for cancer immunotherapy. In order to improve the disadvantages of CAR-T cells in signal transduction, we synthesize a fusion construct (scFv-TCR) that consists of a tumor antigen-specific scFv fused to a TCR subunit (such as the CD3ε subunit). Upon introduction into T cells, the fusion construct is integrated into the TCR complex and leverages the signaling cascade of the complete TCR to kill cancer cells when tumor-specific antigens bind to scFvs. Given that scfv-TCR T cells leverage native TCR signaling instead of artificial signaling of the CAR, this strategy might improve the efficacy of existing CAR-T therapies for solid tumors.
Table.1 Comparison of CAR-T, TCR-T cells, and scFv-TCR T cells
CAR-T cells | TCR-T cells | scFv-TCR T cells | |
Target antigen | Cell surface antigen | Peptide/MHC complex | Cell surface antigen |
Extracellular binding | Tumor antigen-specific scFv | TCR | Tumor antigen-specific scFv |
Intracellular signaling | Artificial signaling | TCR signaling | Entire TCR signaling |
HLA restriction | HLA-Independent | HLA-dependent | HLA-Independent |
In theory, there are several construct strategies since an anti-tumor-specific scFv can be fused to different TCR subunits, for example, TCRα, TCRβ, CD3γ, CD3δ, or CD3ε. The scFv fused to the CD3ε-/γ- subunits is the most common construct. The fusion construct is integrated into the TCR complex to form a functional TCR complex with novel target specificity, triggering a potent anti-tumor response. In addition, different scFv binders can be tethered to CD3ε-/γ- subunits, respectively, and upon integration into the TCR can generate dual targeting T cells.
Fig.1 The natural TCR complex and scfv-TCR fusion constructs.1
Creative Biolabs is committed to supporting the cell therapy field of innovation by bringing together the best science, experience, and technologies. Drawing on our expertise in T-cell therapy development, we offer advanced customization options tailored to your specific needs. We provide a full range of TCR fusion construct-T cell development services, covering the design of scFv-TCR fusion construct, lentiviral production, T cell transduction, in vivo and in vitro functional assays. If you want to make a breakthrough in cancer immunotherapy, please feel free to contact us. Our scientist team is ready to understand your requirements and carry out your project. You will be updated with each stage of the project.
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