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ESMO TAT 2023 | Employing CRISPR technology to enhance tumor control and T-cell fitness

Eliana Ruggiero, PhD, San Raffaele Scientific Institute, Milan, Italy, comments on her work with CRISPR technology in the field of cellular therapy, specifically the modification of T-cells to enhance tumor control and T-cell fitness. Her work focuses on the destruction of the endogenous TCR repertoire using nucleases to remove unwanted specificity on the surface of T-cells, and thus to generate a specialized T-cell army to attack the tumor. While she began using Zinc finger nucleases (ZFNs) for this task, CRISPR technology proved to be more suited to application in clinical settings as the process is completable in a shorter time frame. Further, she has employed CRISPR to overcome immunosuppression in the tumor microenvironment by destroying the inhibitory receptors present on the surface of endogenous T-cells. She has also been experimenting with the insertion method of transgenes, either using viral vectors or targeted integration into a specific genomic segment. From this experimentation she has observed that introduction of TCR transgenes directly into the TCR alpha locus results in a highly efficient T-cell product, especially in vivo. This interview took place at the ESMO Targeted Anticancer Therapies (TAT) Congress 2023 in Paris, France.

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