CRISPR基因组编辑与白血病免疫治疗的未来

BACKGROUND AND AIMS: Leukaemia presents ongoing therapeutic challenges due to relapse and toxicity associated with standard treatments. By enabling more targeted and safer therapies, CRISPR genome editing is emerging as a powerful tool to address these issues.

METHODS: We review current literature on CRISPR technologies in leukaemia immunotherapy, focussing on studies involving four key antigens commonly targeted in leukaemia: CD33, CD7, CD45 and CD19.

RESULTS: We trace the evolution of CRISPR technologies from conventional CRISPR-Cas9 to base editing, highlighting how CRISPR platforms are being repurposed to enhance efficacy and clinical safety. Key studies targeting CD33 demonstrate how editing strategies can enable safer acute myeloid leukaemia (AML) therapies by reducing off-tumour toxicity; those addressing CD7 show how base editing prevents T-cell fratricide in T-cell acute lymphoblastic leukaemia (T-ALL) immunotherapy; studies focusing on CD45 illustrate how targeted editing facilitates universal CAR T-cell therapy; and clinical trials on CD19 support the feasibility of "off-the-shelf" treatments against paediatric B-cell acute lymphoblastic leukaemia (B-ALL).

CONCLUSION: While base editing excels in precision and functional preservation, CRISPR-Cas9 remains preferred when complete gene knockout is desired. As off-tumour toxicity and fratricide are addressed, the future clinical impact of these technologies is poised to expand.