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Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing

Alves, E., Taifour, S., Dolcetti, R., Chee, J., Nowak, A.K., Gaudieri, S. and Blancafort, P. (2021) Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing. Molecular Therapy - Methods & Clinical Development, 21 (11). pp. 592-606.

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Precise clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genetic and epigenetic manipulation of the immune response has become a promising immunotherapeutic approach towards combating tumorigenesis and tumor progression. CRISPR-based immunologic reprograming in cancer therapy comprises the locus-specific enhancement of host immunity, the improvement of tumor immunogenicity and the suppression of tumor immunoevasion. To date, the ex vivo re-engineering of immune cells directed to inhibit the expression of immune checkpoints or to express synthetic immune receptors (chimeric antigen receptor therapy) has shown success in some settings, such as in the treatment of melanoma, lymphoma, liver and lung cancer. However, advancements in nuclease-deactivated CRISPR-associated nuclease-9 (dCas9)-mediated transcriptional activation or repression and Cas13-directed gene suppression presents novel avenues for the development of tumor immunotherapies. In this review, the basis for development, mechanism of action and outcomes from recently published Cas9-based clinical trial (genetic editing) and dCas9/Cas13-based pre-clinical (epigenetic editing) data are discussed. Lastly, we review cancer immunotherapy-specific considerations and barriers surrounding use of these approaches in the clinic.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Elsevier
Copyright: © 2021 The Authors.
United Nations SDGs: Goal 3: Good Health and Well-Being
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