Although chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable success in hematological malignancies, its therapeutic efficacy in solid tumors remains limited by several challenges, including insufficient tumor infiltration, T cell exhaustion and the immunosuppressive tumor microenvironment (TME). CRISPR/Cas, a third-generation gene editing technology developed in recent years, is characterized by its simplicity and high efficiency. This technology has demonstrated broad application potential across multiple fields and has emerged as a powerful tool for improving CAR-T cell therapy. In this review, we summarize recent advances in the application of CRISPR/Cas gene editing technology to enhance the antitumor activity of CAR-T cells against solid tumors. We also discuss the key challenges currently faced and systematically propose potential strategies for overcoming the limitations.
Wenjing Liu, Jiayi Gu, Chenghao Xie et al.· Frontiers in Immunology· 0 citations
For decades, autoimmune disease treatment depended on long-term immunosuppression, which seldom yields lasting immune tolerance and carries cumulative toxic risks. Recent cell therapies, including chimeric antigen receptor (CAR) T cells, regulatory T cells, and mesenchymal stromal cells, have induced deep remission in refractory diseases, often persisting after treatment withdrawal and indicating benefits beyond short-term inflammation suppression. However, traditional dose-exposure-response pharmacokinetic/pharmacodynamic frameworks are insufficient to account for the in vivo expansion, trafficking, and phenotypic evolution of living cellular products. Here we propose that, in autoimmune diseases, cell-based therapies exemplified by CAR T cells should be reframed from exposure-control pharmacology to state-transition pharmacology. Through endogenous expansion and immune networks, therapeutic cells may shift the immune system from a pathological toward a tolerant steady state. Because toxicities may reflect the amplification or persistence of intended mechanisms, future work requires quantitative metrics of immune state transitions and programmable strategies for precise functional control.
Juliang Qin, Guangyu Zhang, Ning Zhao et al.· Annual Review of Pharmacolog...· 0 citations