Applications of CRISPR Genome Editing to Advance the Next Generation of Adoptive Cell Therapies for Cancer

Adoptive cell therapy (ACT) for cancer shows tremendous potential; however, sev- eral 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.

Automated summary

Adoptive cell therapy for cancer has shown great potential, but faces challenges including poor T-cell function and lack of target antigens. Innovative genome-editing strategies, particularly using CRISPR, are addressing these limitations and advancing the next generation of cell therapy products. The clinical impact of ACT for cancer can be enhanced through specific genetic modifications and high-throughput CRISPR screens for novel therapy targets.