Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing

被引:0
|
作者
Alexander Dimitri
Friederike Herbst
Joseph A. Fraietta
机构
[1] University of Pennsylvania,Department of Microbiology, Perelman School of Medicine
[2] University of Pennsylvania,Center for Cellular Immunotherapies, Perelman School of Medicine
[3] University of Pennsylvania,Abramson Cancer Center, Perelman School of Medicine
[4] National Center for Tumor Diseases,Department of Translational Medical Oncology
[5] Dresden and German Cancer Research Center,Department of Pathology and Laboratory Medicine, Perelman School of Medicine
[6] University of Pennsylvania,undefined
来源
Molecular Cancer | / 21卷
关键词
CRISPR; CAR T-cell; Gene editing; Immunotherapy; Cancer;
D O I
暂无
中图分类号
学科分类号
摘要
Chimeric Antigen Receptor (CAR) T-cells represent a breakthrough in personalized cancer therapy. In this strategy, synthetic receptors comprised of antigen recognition, signaling, and costimulatory domains are used to reprogram T-cells to target tumor cells for destruction. Despite the success of this approach in refractory B-cell malignancies, optimal potency of CAR T-cell therapy for many other cancers, particularly solid tumors, has not been achieved. Factors such as T-cell exhaustion, lack of CAR T-cell persistence, cytokine-related toxicities, and bottlenecks in the manufacturing of autologous products have hampered the safety, effectiveness, and availability of this approach. With the ease and accessibility of CRISPR-Cas9-based gene editing, it is possible to address many of these limitations. Accordingly, current research efforts focus on precision engineering of CAR T-cells with conventional CRISPR-Cas9 systems or novel editors that can install desired genetic changes with or without introduction of a double-stranded break (DSB) into the genome. These tools and strategies can be directly applied to targeting negative regulators of T-cell function, directing therapeutic transgenes to specific genomic loci, and generating reproducibly safe and potent allogeneic universal CAR T-cell products for on-demand cancer immunotherapy. This review evaluates several of the ongoing and future directions of combining next-generation CRISPR-Cas9 gene editing with synthetic biology to optimize CAR T-cell therapy for future clinical trials toward the establishment of a new cancer treatment paradigm.
引用
收藏
相关论文
共 50 条
  • [31] CRISPR/Cas9 Systems: The Next Generation Gene Targeted Editing Tool
    Guo S.
    Lv Y.
    Lin Y.
    Lin K.
    Peng P.
    Wu Y.
    Peng J.
    Song S.
    Li Z.
    Liu Q.
    Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, 2015, 85 (2) : 377 - 387
  • [32] CRISPR-Cas9 gene editing of inhibitory receptor signaling pathways improves CAR T cell activity against glioblastoma
    Sanber, Khaled
    Nawas, Zeid
    Salsman, Vita
    Gad, Ahmed
    Matthew, Pretty Rose
    Landi, Daniel
    Lee, Ciaran
    Sengal, Amel
    Chakraborty, Rikhia
    Joseph, Sujith
    Nabil, Ahmed
    Hegde, Meenakshi
    CANCER RESEARCH, 2020, 80 (16)
  • [33] Gene Editing in Trypanosomatids: Tips and Tricks in the CRISPR-Cas9 Era
    Yagoubat, Akila
    Corrales, Rosa M.
    Bastien, Patrick
    Leveque, Maude F.
    Sterkers, Yvon
    TRENDS IN PARASITOLOGY, 2020, 36 (09) : 745 - 760
  • [34] CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
    Norton, Mary E.
    OBSTETRICAL & GYNECOLOGICAL SURVEY, 2021, 76 (06) : 327 - 329
  • [35] Alzheimer disease mice improve with CRISPR-Cas9 gene editing
    Fyfe, Ian
    NATURE REVIEWS NEUROLOGY, 2019, 15 (05) : 247 - 247
  • [36] Gene Editing with Crispr-Cas9 for Treating Beta-Hemoglobinopathies
    Lee, Ciaran
    Bao, Gang
    Porteus, Matthew H.
    Cornu, Tatjana
    Miccio, Annarita
    Cradick, Thomas
    Cathomen, Toni
    Lundberg, Ante
    Mavilio, Fulvio
    BLOOD, 2015, 126 (23)
  • [37] CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
    Haydar Frangoul
    四川生理科学杂志, 2020, 42 (04) : 506 - 506
  • [38] Gene Editing and Crop Improvement Using CRISPR-Cas9 System
    Arora, Leena
    Narula, Alka
    FRONTIERS IN PLANT SCIENCE, 2017, 8
  • [39] CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
    Frangoul, H.
    Altshuler, D.
    Cappellini, M. D.
    Chen, Y-S
    Domm, J.
    Eustace, B. K.
    Foell, J.
    de la Fuente, J.
    Grupp, S.
    Handgretinger, R.
    Ho, T. W.
    Kattamis, A.
    Kernytsky, A.
    Lekstrom-Himes, J.
    Li, A. M.
    Locatelli, F.
    Mapara, M. Y.
    de Montalembert, M.
    Rondelli, D.
    Sharma, A.
    Sheth, S.
    Soni, S.
    Steinberg, M. H.
    Wall, D.
    Yen, A.
    Corbacioglu, S.
    NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (03): : 252 - 260
  • [40] Reversible RNA acylation for control of CRISPR-Cas9 gene editing
    Habibian, Maryam
    McKinlay, Colin
    Blake, Timothy R.
    Kietrys, Anna M.
    Waymouth, Robert M.
    Wender, Paul A.
    Kool, Eric T.
    CHEMICAL SCIENCE, 2020, 11 (04) : 1011 - 1016