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Nanoparticles-Mediated CRISPR-Cas9 systems for CAR T-cell immunotherapy as smart cancer biotherapeutics
DOI:10.1016/j.jiec.2025.06.017.png)
Abstract
En 中文
The spread of cancer among human societies and the subsequent mortalities necessitates the development of intelligent cancer treatment methodologies with negligible side effects. Therefore, immunotherapy to cure victims with hematologic malignancies that have recently been approved, labeled as “chimeric antigen receptor (CAR) T-cell therapy”, was successfully developed with outstanding outcomes. However, CAR T-cell therapy still suffers from numerous safety challenges due to a lack of control over the location and exposure time of the anti-tumor immune effect and the prospective for off-target toxicity. This work aims to describe the design and development of light-switchable (liCAR) T-cells capable of precisely being activated for the real-time elimination of cancer cells. The development of intelligent targeting is accompanied by the emergence of the clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system. Notably, CRISPR-Cas9 allows multiplex genome editing, enabling the simultaneous targeting of multiple genomic loci. This capability has been successfully applied in cancer immunotherapy, for instance, to knock out multiple immune checkpoint regulators such as PD-1, CTLA-4, and LAG-3 in CAR T-cells, thereby improving their anti-tumor activity. Indeed, the gene therapy field has undergone a profound revolution thanks to this system. Consequently, it is crucial to guarantee that the CRISPR-Cas9 components are delivered efficaciously into the intricate three-dimensional (3D) structures of human retinal tissue to achieve successful gene editing. Nanoparticles (NPs) have been a critical component of recent technological advances in nanomedicine, enabling CRISPR-Cas9 to deliver its therapeutic agents with high efficiency, substantially improving its therapeutic potential. The significant progress in NP technology has resulted in the emergence of novel opportunities for gene therapy, therefore presenting a very encouraging approach for addressing illnesses and disorders by targeting the genetic level. Overall, this review focuses on smart cancer immunotherapy techniques by providing a combined perspective of nanotechnology and genome editing by considering the challenges and gaps in this field.
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