Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9

被引:9
作者
Amiri, Maryam [1 ]
Moaveni, Amir Kian [1 ]
Zolbin, Masoumeh Majidi [1 ]
Shademan, Behrouz [2 ]
Nourazarian, Alireza [3 ]
机构
[1] Univ Tehran Med Sci, Pediat Urol & Regenerat Med Res Ctr, Childrens Med Ctr, Tehran, Iran
[2] Shiraz Univ Med Sci, Sch Paramed Sci, Med Journalism, Shiraz, Iran
[3] Khoy Univ Med Sci, Dept Basic Med Sci, Khoy, Iran
关键词
CAR-T cell therapy; CRISPR/Cas9; technology; immunotherapy; genetic engineering; personalized cancer treatment; CHIMERIC-ANTIGEN-RECEPTOR; HOMOLOGY-DIRECTED REPAIR; CRISPR-CAS9; CAS9; TARGET; SPECIFICITY; GENERATION; MALIGNANCY; LEUKEMIA; EFFICACY;
D O I
10.3389/fimmu.2024.1462697
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:18
相关论文
共 152 条
[121]   CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome [J].
Shin, Ha Youn ;
Wang, Chaochen ;
Lee, Hye Kyung ;
Yoo, Kyung Hyun ;
Zeng, Xianke ;
Kuhns, Tyler ;
Yang, Chul Min ;
Mohr, Teresa ;
Liu, Chengyu ;
Hennighausen, Lothar .
NATURE COMMUNICATIONS, 2017, 8
[122]   Rationally engineered Cas9 nucleases with improved specificity [J].
Slaymaker, Ian M. ;
Gao, Linyi ;
Zetsche, Bernd ;
Scott, David A. ;
Yan, Winston X. ;
Zhang, Feng .
SCIENCE, 2016, 351 (6268) :84-88
[123]   RS-1 enhances CRISPR/Cas9-and TALEN-mediated knock-in efficiency [J].
Song, Jun ;
Yang, Dongshan ;
Xu, Jie ;
Zhu, Tianqing ;
Chen, Y. Eugene ;
Zhang, Jifeng .
NATURE COMMUNICATIONS, 2016, 7
[124]   Chimeric antigen receptor (CAR) T-cell therapy: Harnessing extracellular vesicles for enhanced efficacy [J].
Spokeviciute, Beatrice ;
Kholia, Sharad ;
Brizzi, Maria Felice .
PHARMACOLOGICAL RESEARCH, 2024, 208
[125]   CRISPR-engineered T cells in patients with refractory cancer [J].
Stadtmauer, Edward A. ;
Fraietta, Joseph A. ;
Davis, Megan M. ;
Cohen, Adam D. ;
Weber, Kristy L. ;
Lancaster, Eric ;
Mangan, Patricia A. ;
Kulikovskaya, Irina ;
Gupta, Minnal ;
Chen, Fang ;
Tian, Lifeng ;
Gonzalez, Vanessa E. ;
Xu, Jun ;
Jung, In-young ;
Melenhorst, J. Joseph ;
Plesa, Gabriela ;
Shea, Joanne ;
Matlawski, Tina ;
Cervini, Amanda ;
Gaymon, Avery L. ;
Desjardins, Stephanie ;
Lamontagne, Anne ;
Salas-Mckee, January ;
Fesnak, Andrew ;
Siegel, Donald L. ;
Levine, Bruce L. ;
Jadlowsky, Julie K. ;
Young, Regina M. ;
Chew, Anne ;
Hwang, Wei-Ting ;
Hexner, Elizabeth O. ;
Carreno, Beatriz M. ;
Nobles, Christopher L. ;
Bushman, Frederic D. ;
Parker, Kevin R. ;
Qi, Yanyan ;
Satpathy, Ansuman T. ;
Chang, Howard Y. ;
Zhao, Yangbing ;
Lacey, Simon F. ;
June, Carl H. .
SCIENCE, 2020, 367 (6481) :1001-+
[126]   A novel full-human CD22-CAR T cell therapy with potent activity against CD22low B-ALL [J].
Tan, Yue ;
Cai, Haodong ;
Li, Chuo ;
Deng, Biping ;
Song, Weiliang ;
Ling, Zhuojun ;
Hu, Guang ;
Yang, Yongkun ;
Niu, Panpan ;
Meng, Guangrong ;
Cheng, Wei ;
Xu, Jinlong ;
Duan, Jiajia ;
Wang, Zelin ;
Yu, Xinjian ;
Feng, Xiaoming ;
Zhou, Jianfeng ;
Pan, Jing .
BLOOD CANCER JOURNAL, 2021, 11 (04)
[127]   Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology [J].
Tao, Ruiyu ;
Han, Xiaopeng ;
Bai, Xue ;
Yu, Jianping ;
Ma, Youwei ;
Chen, Weikai ;
Zhang, Dawei ;
Li, Zhengkai .
FRONTIERS IN IMMUNOLOGY, 2024, 15
[128]  
Tashiro Haruko, 2024, Rinsho Ketsueki, V65, P644, DOI 10.11406/rinketsu.65.644
[129]   Technology developments in biological tools for targeted genome surgery [J].
Teimourian, Shahram ;
Abdollahzadeh, Rasoul .
BIOTECHNOLOGY LETTERS, 2015, 37 (01) :29-39
[130]   The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity [J].
Thistlethwaite, Fiona C. ;
Gilham, David E. ;
Guest, Ryan D. ;
Rothwell, Dominic G. ;
Pillai, Manon ;
Burt, Deborah J. ;
Byatte, Andrea J. ;
Kirillova, Natalia ;
Valle, Juan W. ;
Sharma, Surinder K. ;
Chester, Kerry A. ;
Westwood, Nigel B. ;
Halford, Sarah E. R. ;
Nabarro, Stephen ;
Wan, Susan ;
Austin, Eric ;
Hawkins, Robert E. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2017, 66 (11) :1425-1436