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What is SCID cloning2/7/2024 According to the previous strategies, an scFv with high binding capacity to a target antigen is likely to be selected for a CAR construct, and then the reactivity of CAR-T cells expressing the scFv should be further assessed. Basically, using conventional methods, identification of antitumor scFvs seems to require 10 8–10 10 library sources of variable regions derived from immunoglobulin 22, 23, 24. In contrast, optimization of variable regions in a single chain fragment variable (scFv) for CAR-T cells has yet to be studied well, even though an scFv plays an important role in the recognition of a target antigen. To optimize CAR signaling for activating and maintaining T-cell functions, a series of studies focusing on manipulating spacer sequences 11, 12, 13, and the intracellular domains 14, 15, 16, 17, 18, 19, 20, 21 of a CAR construct have been performed. These clinical trials suggest that the expansion and persistence of CAR-T cells appear to be important to achieve durable clinical responses 9, 10. Similar content being viewed by othersĬhimeric antigen receptor (CAR)-redirected T cells display antitumor reactivity, and clinical trials of CAR-T-cell therapy demonstrated prolonged survival in patients with refractory CD19-positive malignancies 1, 2, 3, 4, 5, 6, 7, 8. This system may allow us to adjust an immunological synapse formed by an scFv expressed by CAR-T cells and a target antigen, representing an ideal form of CAR-T-cell immunotherapy. Therefore, the optimization of an scFv is needed to maximize the in vivo antitumor functions of CAR-T cells. Importantly, we have demonstrated that the newly optimized scFv-expressing CAR-T cells had better proliferation capacity and durable phenotypes, enabling superior reactivity against advanced tumors in vivo in comparison with the original CAR-T cells. Using this system, target-specific recognition of CAR-T cells appeared to be finely tuned by selecting a new variable region. Then, scFv library-expressing CAR-T cells were generated and stimulated with target cells to concentrate the antigen-specific population. A variable region library containing the variable and J regions of the human immunoglobulin light or heavy chain was fused with the variable region of a heavy or light chain encoded by an existing tumor-specific antibody to generate a new scFv library. We have established a single-chain antibody (scFv) generation system in which scFv library-expressing CAR-T cells can be screened appropriately based on their antitumor functions. Cancer immunotherapy using T cells redirected with chimeric antigen receptor (CAR) has shown a lot of promise.
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