Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Medical Journalism, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Front Immunol. 2024 Nov 8;15:1462697. doi: 10.3389/fimmu.2024.1462697. eCollection 2024.
Optimizing cancer treatment has become a pivotal goal in modern oncology, with advancements in immunotherapy and genetic engineering offering promising avenues. CAR-T cell therapy, a revolutionary approach that harnesses the body's own immune cells to target and destroy cancer cells, has shown remarkable success, particularly in treating acute lymphoblastic leukemia (ALL), and in treating other hematologic malignancies. While CAR-T cell therapy has shown promise, challenges such as high cost and manufacturing complexity remain. However, its efficacy in solid tumors remains limited. The integration of CRISPR/Cas9 technology, a powerful and precise genome-editing tool, also raises safety concerns regarding unintended edits and off-target effects, offers a synergistic potential to overcome these limitations. CRISPR/Cas9 can enhance CAR-T cell therapy by improving the specificity and persistence of CAR-T cells, reducing off-target effects, and engineering resistance to tumor-induced immunosuppression. This combination can also facilitate the knockout of immune checkpoint inhibitors, boosting the anti-tumor activity of CAR-T cells. Recent studies have demonstrated that CRISPR/Cas9-edited CAR-T cells can target previously untreatable cancer types, offering new hope for patients with refractory cancers. This synergistic approach not only enhances the efficacy of cancer treatment but also paves the way for personalized therapies tailored to individual genetic profiles. This review highlights the ongoing research efforts to refine this approach and explores its potential to revolutionize cancer treatment across a broader range of malignancies. As research progresses, the integration of CAR-T cell therapy and CRISPR/Cas9 holds the promise of transforming cancer treatment, making it more effective and accessible. This review explores the current advancements, challenges, and future prospects of this innovative therapeutic strategy.
优化癌症治疗已成为现代肿瘤学的关键目标，免疫疗法和基因工程的进步提供了有前途的途径。嵌合抗原受体 T 细胞（CAR-T）疗法是一种利用人体自身免疫细胞靶向和破坏癌细胞的革命性方法，已显示出显著的疗效，特别是在治疗急性淋巴细胞白血病（ALL）和治疗其他血液恶性肿瘤方面。虽然 CAR-T 细胞疗法显示出了前景，但仍存在成本高和制造复杂等挑战。然而，其在实体肿瘤中的疗效仍然有限。CRISPR/Cas9 技术是一种强大而精确的基因组编辑工具，其整合也引发了对意外编辑和脱靶效应的安全性担忧，为克服这些限制提供了协同潜力。CRISPR/Cas9 可以通过提高 CAR-T 细胞的特异性和持久性、降低脱靶效应以及设计对肿瘤诱导的免疫抑制的抗性，来增强 CAR-T 细胞疗法。这种组合还可以促进免疫检查点抑制剂的敲除，增强 CAR-T 细胞的抗肿瘤活性。最近的研究表明，CRISPR/Cas9 编辑的 CAR-T 细胞可以靶向以前无法治疗的癌症类型，为难治性癌症患者带来了新的希望。这种协同方法不仅提高了癌症治疗的疗效，还为针对个体遗传特征的个性化治疗铺平了道路。这篇综述强调了正在进行的研究努力，以完善这种方法，并探讨了其在更广泛的恶性肿瘤治疗中带来变革的潜力。随着研究的进展，CAR-T 细胞疗法和 CRISPR/Cas9 的整合有望改变癌症治疗，使其更有效且更易获得。本综述探讨了这种创新治疗策略的当前进展、挑战和未来前景。
