CRISPR Genome Editing Advances Next-Generation Adoptive Cell Therapies for Cancer
This review provides a comprehensive overview of CRISPR applications in adoptive cell therapy, including knockout of inhibitory receptors, insertion of synthetic receptors, and generation of allogeneic off-the-shelf products. High-throughput CRISPR screens have identified novel targets for enhancing T-cell potency in hostile tumour microenvironments. The manufacturing and quality control of CRISPR-edited cell products require specialised molecular assays including on-target editing efficiency and off-target analysis by sequencing.
The original study
Applications of CRISPR Genome Editing to Advance the Next Generation of Adoptive Cell Therapies for Cancer.
- Authors
- Fix SM, Jazaeri AA, Hwu P
- Journal
- Cancer discovery
- Type
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
- PMID
- 33563662
Original abstract
Adoptive cell therapy (ACT) for cancer shows tremendous potential; however, several challenges preclude its widespread use. These include poor T-cell function in hostile tumor microenvironments, a lack of tumor-specific target antigens, and the high cost and poor scalability of cell therapy manufacturing. Creative genome-editing strategies are beginning to emerge to address each of these limitations, which has initiated the next generation of cell therapy products now entering clinical trials. CRISPR is at the forefront of this revolution, offering a simple and versatile platform for genetic engineering. This review provides a comprehensive overview of CRISPR applications that have advanced ACT. SIGNIFICANCE: The clinical impact of ACT for cancer can be expanded by implementing specific genetic modifications that enhance the potency, safety, and scalability of cellular products. Here we provide a detailed description of such genetic modifications, highlighting avenues to enhance the therapeutic efficacy and accessibility of ACT for cancer. Furthermore, we review high-throughput CRISPR genetic screens that have unveiled novel targets for cell therapy enhancement.