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Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
Open accessAbstract
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing. Recent advances in genome editing enable efficient sequence-specific interventions in human cells, including targeted gene delivery to the CCR5 and AAVS1 loci. Here we show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia. We further demonstrate that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion. These findings uncover facets of CAR immunobiology and underscore the potential of CRISPR/Cas9 genome editing to advance immunotherapies.
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“AAV6 homologous donor DNA templates are an efficient way to deliver donor templates for sensitive primary immune cells, including HSPCs and T-Cells15,35–40.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [39]
Experimental — accuracy not yet measuredIn the citing paper
“More recent work has revealed potential advantages of targeted integrations of antigen receptor genes into defined genomic loci (Eyquem et al., 2017), which can be achieved with programmable nucleases such as CRISPR-Cas9 along with viral or non-viral knock-in templates (Gwiazda et al., 2016; Eyquem et al., 2017; Roth et al., 2018).”
From Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies (2020) · cites this paper as Eyquem et al., 2017
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Citations
Cites
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Brentjens, R. J., Davila, M. L., Riviere, I., Park, J., Wang, X., Cowell, L. G., Bartido, S., Stefanski, J., Taylor, C., Olszewska, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005930 · Cited by 2,063
Self-citationBlackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
A human memory T cell subset with stem cell–like properties
Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R., Gostick, E., Yu, Z., Carpenito, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2446 · Cited by 1,974
Long, A. H., Haso, W. M., Shern, J. F., Wanhainen, K. M., Murgai, M., Ingaramo, M., Smith, J. P., Walker, A. J., Kohler, M. E., Venkateshwara, V. R., et al. (2015) · Nature Medicine · doi:10.1038/nm.3838 · Cited by 1,815
Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ /CD28 receptor
Maher, J. F., Brentjens, R. J., Gunset, G., Rivière, I., & Sadelain, M. (2002) · Nature Biotechnology · doi:10.1038/nbt0102-70 · Cited by 1,031
Self-citationBiology and Applications of CRISPR Systems: Harnessing Nature’s Toolbox for Genome Engineering
Wright, A. V., Nuñez, J. K., & Doudna, J. A. (2016) · Cell · doi:10.1016/j.cell.2015.12.035 · Cited by 989
Sommermeyer, D., Hudecek, M., Kosasih, P. L., Gogishvili, T., Maloney, D. G., Turtle, C. J., & Riddell, S. R. (2015) · Leukemia · doi:10.1038/leu.2015.247 · Cited by 890
Zhao, Z., Condomines, M., van der Stegen, S. J. C., Perna, F., Kloss, C. C., Gunset, G., Plotkin, J., & Sadelain, M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.09.004 · Cited by 843
Self-citationTolerance and exhaustion: defining mechanisms of T cell dysfunction
Schietinger, A., & Greenberg, P. D. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.10.001 · Cited by 704
Cited by
Sorted by citations
Items 701–800 of 1,002
Zhang, T., Tan, S., Tang, N., Li, Y., Zhang, C., Sun, J., Guo, Y., Gao, H., Cai, Y., Sun, W. H., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.007 · Cited by 32
Lipid nanoparticles: a promising tool for nucleic acid delivery in cancer immunotherapy
Abaza, T., Mohamed, E., & Zaky, M. Y. (2025) · Medical Oncology · doi:10.1007/s12032-025-02939-3 · Cited by 35
“In cancer immunotherapy, CRISPR has been utilized for producing disease models [204–206], identifying targets [207], and engineering immune cells [208–211].”
Ward, D. E., Fay, B. L., Adejuwon, A. O., Han, H., & Ma, Z. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02231 · Cited by 30
“The risk of insertion-related oncogenesis may be fully addressed by targeting CARs to a harmless location through genome editing (53, 54).”
BackgroundMethodCRISPR-Cas9, A Promising Therapeutic Tool for Cancer Therapy: A Review
Akram, F., Haq, I. U., Ahmed, Z., Khan, H. A., & Ali, M. S. (2020) · Protein and Peptide Letters · doi:10.2174/0929866527666200407112432 · Cited by 33
Improving the therapeutic index in adoptive cell therapy: key factors that impact efficacy
Wang, E., Cesano, A., Butterfield, L. H., & Marincola, F. M. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001619 · Cited by 30
Sharma, R., Dever, D. P., Lee, C. M., Azizi, A., Pan, Y., Camarena, J., Köhnke, T., Bao, G., Porteus, M. H., & Majeti, R. (2021) · Nature Communications · doi:10.1038/s41467-020-20792-y · Cited by 30
Trendel, N., Krüger, P., Gaglione, S. A., Nguyen, J., Pettmann, J., Sontag, E. D., & Dushek, O. (2021) · Science Signaling · doi:10.1126/scisignal.aay9363 · Cited by 33
Strengthening the CAR‐T cell therapeutic application using CRISPR/Cas9 technology
Nezhad, M. S., Yazdanifar, M., Abdollahpour‐Alitappeh, M., Sattari, A., Seifalian, A. M., & Bagheri, N. (2021) · Biotechnology and Bioengineering · doi:10.1002/bit.27882 · Cited by 30
“Hence, this study depicted that how by genome editing technology, a T cell-based therapy can be improved and yield a robust treatment (Eyquem et al., 2017).”
The Application of CRISPR/Cas9 Technology for Cancer Immunotherapy: Current Status and Problems
Wang, L., Chen, Y., Liu, X., Li, Z., & Dai, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.704999 · Cited by 34
“reported that directing a CD19-specific CAR into the T-cell receptor a constant (TRAC) locus by electroporation of Cas9 mRNA and sgRNA not only results in uniform CAR expression, but also enhances T-cell potency in an acute lymphoblastic leukaemia (ALL) mouse model (75).”
BackgroundResearch Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors
Nie, D., Guo, T., Yue, M., Li, W., Zong, X., Zhu, Y., Huang, J., & Lin, M. (2022) · Biomolecules · doi:10.3390/biom12091239 · Cited by 33
CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo
Wu, J., Zou, Z., Liu, Y., Liu, X., Zhangding, Z., Xu, M., & Hu, J. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac887 · Cited by 30
“…TCR or CAR T cells, termed allogeneic T cells, were generated by simultaneously disrupting endogenous TCRs, beta-2 microglobulin (B2M) and programmed cell death protein 1 (PD-1) via CRISPR / Cas9-mediated genome editing (4,10–12), which may greatly extend the application of adoptive T-cell therapy.”
Naeem, M., Hazafa, A., Bano, N., Ali, R., Farooq, M., Razak, S. I. A., Lee, T. Y., & Devaraj, S. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121409 · Cited by 32
Novel extragenic genomic safe harbors for precise therapeutic T cell engineering
Odak, A., Yuan, H., Feucht, J., Cantu, A., Mansilla‐Soto, J., Kogel, F., Eyquem, J., Everett, J. K., Bushman, F. D., Leslie, C. S., et al. (2023) · Blood · doi:10.1182/blood.2022018924 · Cited by 28
Self-citationEvolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures
Majumder, A. (2023) · Cancers · doi:10.3390/cancers16010039 · Cited by 35
“After the CRISPR system was developed, this gene-editing tool was used to make CAR-T cells in 2017 [39].”
MethodCook, P. J., Yang, S. J., Uenishi, G. I., Grimm, A., West, S. E., Wang, L., Jacobs, C., Repele, A., Drow, T., Boukhris, A., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.04.021 · Cited by 30
Activation-inducible CAR expression enables precise control over engineered CAR T cell function
Fräßle, S. P., Tschulik, C., Effenberger, M. J. P., Cletiu, V., Gerget, M., Schober, K., Busch, D. H., Germeroth, L., Stemberger, C., & Poltorak, M. P. (2023) · Communications Biology · doi:10.1038/s42003-023-04978-w · Cited by 30
“It has been demonstrated that better targeting of CARs and engineered TCRs brings clear bene fi ts to the potency and function of edited T cells by inserting arti fi cial genes under control of endogenous TCR promoters thus providing a more physiological (trans-)gene expression 12 .”
Chimeric antigen receptor Treg therapy in transplantation
Eskandari, S. K., Daccache, A., & Azzi, J. R. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.11.005 · Cited by 30
Nix, M. A., & Wiita, A. P. (2024) · Cytotherapy · doi:10.1016/j.jcyt.2024.02.024 · Cited by 30
Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies
Xiang, M., Li, H., Zhan, Y., Ma, D., Gao, Q., & Fang, Y. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01987-z · Cited by 29
“Enabled by CRISPR genome editing, CD19-specific CAR is delivered to the T-cell receptor α constant (TRAC) locus, which results in enhanced T cell activity and slows the development of T cell exhaustion [53].”
BackgroundHarnessing the evolving CRISPR/Cas9 for precision oncology
Li, T., Li, S., Kang, Y., Zhou, J., & Yi, M. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05570-4 · Cited by 35
“Eyquem et al. utilized the HDR feature of the CRISPR/Cas9 tool to achieve targeted gene insertion of large DNA sequences, successfully integrating a CD-19 specific CAR into the TRAC locus, which encodes the T-cell receptor (TCR) α chain [169].”
MethodLi, Y.-R., Zhou, K., Lee, D., Zhu, Y., Halladay, T., Yu, J., Zhou, Y., Lyu, Z., Fang, Y., Chen, Y., et al. (2025) · Nature Protocols · doi:10.1038/s41596-024-01077-w · Cited by 30
“59.”
Tang, S., Chen, X., Tong, X., & Zhu, L. (2025) · International Journal of Medical Sciences · doi:10.7150/ijms.112724 · Cited by 31
“The resulting modified T-cells exhibited enhanced safety, precision, and therapeutic effectiveness in selectively eliminating acute lymphoblastic leukemia cells compared to earlier CAR T-cell designs [193].”
Advancements in CRISPR/Cas9 technology—Focusing on cancer therapeutics and beyond
Mirza, Z., & Karim, S. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.026 · Cited by 29
Kojima, R., Aubel, D., & Fussenegger, M. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03486-y · Cited by 29
Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity
Hajeri, P. B., Sharma, N., & Yamamoto, M. (2020) · Cancers · doi:10.3390/cancers12061504 · Cited by 30
Targeted Cellular Micropharmacies: Cells Engineered for Localized Drug Delivery
Gardner, T. J., Bourne, C. M., Dacek, M. M., Kurtz, K. G., Malviya, M., Peraro, L., Silberman, P. C., Vogt, K. C., Unti, M. J., Brentjens, R. J., et al. (2020) · Cancers · doi:10.3390/cancers12082175 · Cited by 29
“Tumor antigen specificity can be assigned to iPSCs or T-iPSCs and their T cell derivatives by introducing exogenous TCR or CAR transgenes [70,71].”
BackgroundAdvances in chimeric antigen receptor T cells
Beyar‐Katz, O., & Gill, S. I. (2020) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000614 · Cited by 29
“This effectively excludes use of mRNA or of nonintegrating viruses such as AAV, except as the vehicles for genetic editing tools such as nucleases [19,20] or transposon/transposases [21,22].”
BackgroundUsing CRISPR to enhance T cell effector function for therapeutic applications
Heeren, J. J. F. (2020) · Cytokine X · doi:10.1016/j.cytox.2020.100049 · Cited by 31
“This can be achieved by the (viral) integration of a traditional T cell receptor (TCR) [28 29], or a Chimeric Antigen Receptor (CAR) [30].”
BackgroundDing, R., Long, J., Yuan, M., Jin, Y., Yang, H., Chen, M., Chen, S., & Duan, G. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.639108 · Cited by 32
Better by design: What to expect from novel CAR-engineered cell therapies?
Luginbuehl, V., Abraham, E., Kovar, K., Flaaten, R., & Müller, A. M. S. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.107917 · Cited by 29
Beider, K., Itzhaki, O., Schachter, J., Grushchenko-Polaq, A. H., Voevoda-Dimenshtein, V., Rosenberg, E., Ostrovsky, O., Devillers, O., Frommer, R. S., Zeltzer, L., et al. (2022) · Cells · doi:10.3390/cells11071140 · Cited by 30
“T cell exhaustion has been implicated as an important factor limiting the efficacy of CAR T cells against cancer [5,6].”
BackgroundChimeric antigen receptor T cells applied to solid tumors
Zhou, Z., Tao, C., Li, J., Tang, J. C. O., Chan, A. S. C., & Zhou, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.984864 · Cited by 29
“Modification of endogenous promoters and epigenetic can also be utilized to prevent T cell exhaustion (55).”
BackgroundModeling Patient-Specific CAR-T Cell Dynamics: Multiphasic Kinetics via Phenotypic Differentiation
Paixão, E. A., Barros, L. R. C., Fassoni, A. C., & Almeida, R. C. (2022) · Cancers · doi:10.3390/cancers14225576 · Cited by 30
Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells
Zhang, Y., Fang, H., Wang, G., Yuan, G., Dong, R., Luo, J., Lyu, Y., Wang, Y., Li, P., Zhou, C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-44176-0 · Cited by 32
“The high selectivity for TRAC locus integration and the low potential off-target hotspots have been validated previously, con fi rming the precision of CRISPR/Cas9 mediated genome editing method used 17,19 .”
InfluentialOff the shelf T cell therapies for hematologic malignancies
McCreedy, B. J., Senyukov, V., & Nguyen, K. T. (2018) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2018.03.001 · Cited by 31
Inserting EF1α-driven CD7-specific CAR at CD7 locus reduces fratricide and enhances tumor rejection
Jiang, J., Chen, J., Liao, C., Duan, Y., Wang, Y., Shang, K., Huang, Y., Tang, Y., Gao, X., Gu, Y., et al. (2023) · Leukemia · doi:10.1038/s41375-023-01948-3 · Cited by 28
“In the previous study, TRAC CD19 CAR under EF1α control made T cells express higher CAR but showed inferior in vivo anti-tumor activity than TRAC CD19 CAR under TRAC intrinsic promotor control [28].”
BackgroundResultInfluentialmRNA-based therapeutic strategies for cancer treatment
Taibi, T., Cheon, S., Perna, F., & Vu, L. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.04.035 · Cited by 31
Mechanism-guided engineering of a minimal biological particle for genome editing
Ngo, W., Peukes, J., Baldwin, A., Xue, Z. W., Hwang, S., Stickels, R. R., Lin, Z., Satpathy, A. T., Wells, J. A., Schekman, R. W., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2413519121 · Cited by 30
“T cells ( 30 ).”
Integrated epigenetic and genetic programming of primary human T cells
Goudy, L., Ha, A. S., Borah, A. A., Umhoefer, J. M., Chow, L., Tran, C., Winters, A., Talbot, A., Hernandez, R., Li, Z., et al. (2025) · Nature Biotechnology · doi:10.1038/s41587-025-02856-w · Cited by 38
“Targeted insertion of a CAR to the endogenous TCRα constant ( TRAC ) locus using CRISPR–Cas9 genome editing can enhance T cell potency by placing CAR expression under the regulated and dynamic control of the endogenous TCRα promoter, limiting exhaustion and dysfunction 52 .”
Self-citationYakoub‐Agha, I., Ferrand, C., Chalandon, Y., Ballot, C., Castilla‐Llorente, C., Deschamps, M., Gauthier, J., Labalette, M., Larghero, J., Maheux, C., et al. (2017) · Bulletin du Cancer · doi:10.1016/j.bulcan.2017.10.017 · Cited by 30
Advances in Chimeric Antigen Receptor T‐Cell Therapies for Solid Tumors
Baybutt, T. R., Flickinger, J. C., Caparosa, E. M., & Snook, A. E. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1280 · Cited by 28
“Eyquem et al.42 created a CRISPR system to insert the CAR construct within the TCRα chain constant (TRAC) locus, resulting in superior antitumor efficacy.”
Wittsten, A. H., & Roybal, K. T. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.09.005 · Cited by 27
Synthetic Biology in Chimeric Antigen Receptor T (CAR T) Cell Engineering
Zhang, C., Zhuang, Q., Liu, J., & Liu, X. (2022) · ACS Synthetic Biology · doi:10.1021/acssynbio.1c00256 · Cited by 29
Ellis, G. I., Coker, K. E., Winn, D. W., Deng, M. Z., Shukla, D., Bhoj, V. G., Milone, M. C., Wang, W., Liu, C., Naji, A., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100614 · Cited by 29
Ceppi, F., Wilson, A. L., Annesley, C., Kimmerly, G. R., Summers, C. N., Brand, A., Seidel, K. D., Wu, Q. V., Beebe, A., Brown, C., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0501 · Cited by 27
Factors contributing to the potency of CD8+ T cells
Sykulev, Y. K. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.07.005 · Cited by 27
Webber, B. R., Johnson, M. J., Skeate, J. G., Slipek, N. J., Lahr, W. S., DeFeo, A. P., Mills, L. J., Qiu, X., Rathmann, B., Diers, M. D., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01157-4 · Cited by 29
“In addition, site-specific integration is highly desirable, as it improves the safety, consistency and function of engineered cellular products 60 .”
Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy
Shao, W., Yao, Y., Yang, L., Li, X., Ge, T., Zheng, Y., Zhu, Q., Ge, S., Gu, X., Jia, R., et al. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00504-8 · Cited by 30
“The effectiveness of the obtained CAR-T [232] and TCR-T cells for the treatment of hematologic malignancies, some melanomas, and solid tumors such as synovial sarcoma has also been preliminarily demonstrated in mouse models [233, 234] and human clinical trials [235–237].”
BackgroundHIV immune evasin Nef enhances allogeneic CAR T cell potency
Perica, K., Kotchetkov, I. S., Mansilla‐Soto, J., Ehrich, F. D., Herrera, K., Shi, Y., Dobrin, A., Gönen, M., & Sadelain, M. (2025) · Nature · doi:10.1038/s41586-025-08657-0 · Cited by 29
“Graft-versus-host responses occur when donor αβ-T cell receptors (TCRs) recognize host tissue, but can be mitigated by use of T cells lacking an alloreactive TCR 5 or by eliminating TCR expression 6,7 .”
Self-citationChimeric antigen receptor (CAR) T-cell therapy: Engineering immune cells to treat liver diseases
Jaeckel, E., Friedman, S. L., Hudecek, M., & Protzer, U. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.06.007 · Cited by 30
Ma, H.-T., Jeppesen, J. F., & Jaenisch, R. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100097 · Cited by 23
Leveraging Single-Cell Sequencing for Chimeric Antigen Receptor T Cell Therapies
Castellanos-Rueda, R., Roberto, R. B. D., Schlatter, F. S., & Reddy, S. T. (2021) · Trends in biotechnology · doi:10.1016/j.tibtech.2021.03.005 · Cited by 24
Immunotherapies against HER2-Positive Breast Cancer
Duro‐Sánchez, S., Alonso, M. R., & Arribas, J. (2023) · Cancers · doi:10.3390/cancers15041069 · Cited by 29
Synthetic Biology: Immunotherapy by Design
Brenner, J., Cho, J. H., Wong, N. M. L., & Wong, W. W. (2018) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-062117-121147 · Cited by 26
Luan, X., Chen, X., Tang, Y., Zhang, J., Gao, X., Ke, H., Lin, Z., & Zhang, X. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.05.005 · Cited by 28
T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer
Eisenberg, V., Hoogi, S., Shamul, A., Barliya, T., & Cohen, C. J. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.01.007 · Cited by 27
Hunt, M. S., Yang, S. J., Mortensen, E., Boukhris, A., Buckner, J. H., Cook, P. J., & Rawlings, D. J. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.07.016 · Cited by 27
CAR-T cell therapy: a game-changer in cancer treatment and beyond
Utkarsh, K., Srivastava, N., Kumar, S., Khan, A. U., Dagar, G., Kumar, M., Singh, M. K., & Haque, S. (2024) · Clinical & Translational Oncology · doi:10.1007/s12094-023-03368-2 · Cited by 28
“One example of this therapy is the anti-BCMA (B-cell maturation antigen) CAR-T cell therapeutics, which has been shown to have potent activity against multiple myeloma (MM) that is resistant to other therapies [112].”
Advances in manufacturing chimeric antigen receptor immune cell therapies
Ramamurthy, A., Tommasi, A. M., & Saha, K. (2024) · Seminars in Immunopathology · doi:10.1007/s00281-024-01019-4 · Cited by 27
“Additional constraints posed by viral vectors like cost and complexity have resulted in the development of non-viral vectors such as using LNPs for mRNA delivery and CRISPR for gene editing [51–53].”
Menegatti, S., López‐Cobo, S., Galy, A. S. D., Fuentealba, J. R., Silva, L. E., Perrin, L., Heurtebise-Chrétien, S., Pottez-Jouatte, V., Darbois, A., Burgdorf, N., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01282-8 · Cited by 29
“Avoiding graft-versus-host reactions can be achieved by inactivating the T cell receptor α locus 8–11 .”
CAR-T cell therapy for breast cancer: Current status and future perspective
Buono, G., Capozzi, M., Caputo, R., Lauro, V. D., Cianniello, D., Piezzo, M., Cocco, S., Martinelli, C., Verrazzo, A., Tafuro, M., et al. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102868 · Cited by 27
Adeno‐Associated Viral Vectors for Homology‐Directed Generation of CAR‐T Cells
Moço, P. D., Aharony, N., & Kamen, A. (2019) · Biotechnology Journal · doi:10.1002/biot.201900286 · Cited by 28
Development of a Self-Restricting CRISPR-Cas9 System to Reduce Off-Target Effects
Wang, H., Lu, H. A. J., Lei, Y., Gong, C.-Y., Chen, Z., Luan, Y.-Q., Li, Q., Jian, Y.-Z., Wang, H., Wu, F., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.012 · Cited by 27
“The CRISPRCas9 gene knockin function was used to specifically insert the chimeric antigen receptor (CAR) gene targeting CD19 into the T cell receptor alpha chain (TRAC) locus of patients, enhancing the efficacy of CAR-T cells.(12) Recently, the US Food and Drug Administration (FDA) has granted CTX001, which targets fe…”
MethodAbken, H. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.165 · Cited by 27
Gene editing to enhance the efficacy of cancer cell therapies
Murty, T., & Mackall, C. L. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.10.001 · Cited by 25
Krug, A., Martinez-Turtos, A., & Verhoeyen, E. (2021) · Cancers · doi:10.3390/cancers14010183 · Cited by 28
Purcarea, A., Jarosch, S., Barton, J., Grassmann, S. A., Pachmayr, L. O., D’Ippolito, E., Hammel, M., Hochholzer, A., Wagner, K. I., van den Berg, J. H., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abm2077 · Cited by 26
Nasri, M., Mir, P., Dannenmann, B., Amend, D., Skroblyn, T., Xu, Y., Schulze‐Osthoff, K., Klimiankou, M., Welte, K., & Skokowa, J. (2019) · Blood Advances · doi:10.1182/bloodadvances.2017015511 · Cited by 25
“CRISPR/Cas9-mediated gene editing(1,2) has a tremendous potential for clinical applications, such as gene therapy of inherited disorders or boosting of immune cells for cancer immunotherapies.(3-9) Several monogenic disorders, including life-threatening bone marrow failure syndromes, might be treated by CRISPR/Cas9-me…”
BackgroundWang, D., Starr, R., Alizadeh, D., Yang, X., Forman, S. J., & Brown, C. E. (2019) · Journal of Visualized Experiments · doi:10.3791/59275 · Cited by 27
Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies
Dobrin, A., Lindenbergh, P. L., Shi, Y., Perica, K., Xie, H., Jain, N., Chow, A., Wolchok, J. D., Merghoub, T., Sadelain, M., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00744-x · Cited by 23
“To allow for NY-ESO-1-specific TCR delivery into the endogenous TRAC locus using a TCR donor AAV, the complete TCRβ-P2A-TCRα sequence of an NY-ESO-1 TCR (clone Lau 155) was cloned after the splice acceptor site and P2A sequence into the previously described pAAV-TRAC-1928z 37,75 .”
Self-citationStructure and genome editing of type I-B CRISPR-Cas
Lü, M., Yu, C., Zhang, Y., Ju, W., Ye, Z., Hua, C., Mao, J., Hu, C., Yang, Z., & Xiao, Y. (2024) · Nature Communications · doi:10.1038/s41467-024-48598-2 · Cited by 26
“Type I-B CRISPR-Cas3 mediated genome editing in human cells CRISPR/Cas9 engineered T cells showed high ef fi ciency and safety in cancer immunotherapy 46 – 49 , we thereforeexplored the potential usage of Syn CRISPR-Cas3 for genome editing in human cells by disrupting T-cell receptor α constant (…”
Understanding resource competition to achieve predictable synthetic gene expression in eukaryotes
Blasi, R. D., Gabrielli, J., Shabestary, K., Ziarti, I., Ellis, T., Kontoravdi, C., Ledesma‐Amaro, R., & Ceroni, F. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00206-0 · Cited by 28
“For example, integration into the T cell receptor-α constant (TRAC) locus leads to more uniform expression of the CAR, decreased tonic signalling and increased tumour rejection compared with random integration through viral vectors 163 .”
Intelligent Design of Lipid Nanoparticles for Enhanced Gene Therapeutics
Yuan, Y., Li, Y., Li, G., Lei, L., Huang, X., Li, M., & Yao, Y. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00925 · Cited by 28
Exploring CRISPR-Cas: The transformative impact of gene editing in molecular biology
Pandey, V. P., Sharma, S., & Pokharel, Y. R. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102717 · Cited by 29
Cellular therapies: Day by day, all the way
Atilla, E., Kılıç, P., & Gürman, G. (2018) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2018.04.019 · Cited by 25
Gene editing enables T-cell engineering to redirect antigen specificity for potent tumor rejection
Albers, J. J., Ammon, T., Gosmann, D., Audehm, S., Thoene, S., Winter, C., Secci, R., Wolf, A. A., Stelzl, A., Steiger, K., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900367 · Cited by 25
“This region is speci fi cally attractive as it is shared between all rearranged T cells, and a disruption in the fi rst exon is located upstream of the functional region needed for surface expression (Eyquem et al, 2017).”
InfluentialEmerging Immunotherapies against Novel Molecular Targets in Breast Cancer
Sivaganesh, V., Promi, N., Maher, S., & Peethambaran, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052433 · Cited by 25
“Scientists have also used CRISPR to successfully integrate a CD19-specific CAR into the T cell receptor α constant (TRAC) locus, which allowed for robust expression of the CAR and outperformed the function of CARs generated by other methods [32].”
MethodProspects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies
Mazza, R., & Maher, J. F. (2021) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-021-00640-7 · Cited by 26
“Starting material used in this method was either a T-cell clone or an iPSC that had been engineered to express a defined TCR. Notably, introduction of a TCR into an iPSC of non T-cell origin also enhanced T-cell commitment compared to unmodified iPSC.”
BackgroundInfluentialCurrent Limitations and Perspectives of Chimeric Antigen Receptor-T-Cells in Acute Myeloid Leukemia
Maucher, M., Srour, M., Danhof, S., Einsele, H., Hudecek, M., & Yakoub‐Agha, I. (2021) · Cancers · doi:10.3390/cancers13246157 · Cited by 25
Physiological lentiviral vectors for the generation of improved CAR-T cells
Tristán‐Manzano, M., Maldonado‐Pérez, N., Justicia-Lirio, P., Muñoz, P., Cortijo-Gutierréz, M., Pavlovic, K., Jimenez‐Moreno, R., Nogueras, S., Carmona-Luque, M. D., Sánchez-Hernández, S., et al. (2022) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2022.05.003 · Cited by 26
Application of nanotechnology in CAR-T-cell immunotherapy
Zeng, Q., Liu, Z., Niu, T., He, C., Qu, Y., & Qian, Z. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.107747 · Cited by 25
Khan, A. A., & Sarkar, E. (2022) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2022.100641 · Cited by 25
RETRACTED: CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment
Akram, F., Haq, I. U., Sahreen, S., Nasir, N., Naseem, W., Imitaz, M., & Aqeel, A. (2022) · Technology in Cancer Research & Treatment · doi:10.1177/15330338221132078 · Cited by 25
“It consists of an antibody-driven target-binding extracellular domain, a hinge region, a trans-membrane domain, and an intracellular signaling moiety that can activate T-cells.38,39 A CAR-targeted antigen can be recognized by the CAR-bearing altered T-cells, this consequently provokes the proliferation of T-cells, man…”
BackgroundInfluentialRetractedRecent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications
Zhou, L., & Yao, S. (2023) · Molecular Biomedicine · doi:10.1186/s43556-023-00115-5 · Cited by 29
Lau, E. K., Kwong, G., Fowler, T. W., Sun, B.-C., Donohoue, P. D., Davis, R. T., Bryan, M. B., McCawley, S., Clarke, S., Williams, C., et al. (2023) · Cytotherapy · doi:10.1016/j.jcyt.2023.03.011 · Cited by 25
Advances in therapeutic application of CRISPR-Cas9
Sun, J., Wang, J., Zheng, D., & Hu, X. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz031 · Cited by 25
Kalium Nitrat (KNO3): Karakteristik Senyawa dan Transpor IonPreprint
Nurfadilah, K. K., & Zainul, R. (2019) · doi:10.31227/osf.io/dr8ef · Cited by 25
Fang, M., Allen, A. G., Luo, C., & Finn, J. D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1457629 · Cited by 26
Arunachalam, A. K., Grégoire, C., de Oliveira, B. C., & Melenhorst, J. J. (2024) · Blood Reviews · doi:10.1016/j.blre.2024.101241 · Cited by 27
Chimeric antigen receptor T-cells for B-cell malignancies
Lichtman, E. I., & Dotti, G. (2017) · Translational research · doi:10.1016/j.trsl.2017.06.011 · Cited by 23
Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells
Kamrani, A., Mehdizadeh, A., Ahmadi, M., Maleki, L. A., & Yousefi, M. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1602608 · Cited by 24
“Recent studies have reported the destruction and impairment of tumor surface antigens and the presence of a suppressive immune system microenvironment due to the tumor cells heterogeneity [93].”
BackgroundAbramson, J. S., Lunning, M. A., & Palomba, M. L. (2019) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_238693 · Cited by 24
Immune Modulation in Lung Cancer: Current Concepts and Future Strategies
Gaissmaier, L., & Christopoulos, P. (2020) · Respiration · doi:10.1159/000510385 · Cited by 24
Stikvoort, A., van der Schans, J., Sarkar, S., Poels, R., Ruiter, R. W. J., Naik, J., Yuan, H., de Bruijn, J. D., van de Donk, N. W. C. J., Zweegman, S., et al. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000596 · Cited by 25
Advances in Adoptive Cell Therapy Using Induced Pluripotent Stem Cell-Derived T Cells
Netsrithong, R., & Wattanapanitch, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.759558 · Cited by 24
“In addition, if the iPSCs are genetically engineered using September 2021 | Volume 12 | Article 759558 the CRISPR/Cas9 system, the off-target activity from the incorrect binding of sgRNA can often occur and result in insertion-deletion (indel) mutations.”
BackgroundInfluentialGenome edited B cells: a new frontier in immune cell therapies
Rogers, G. L., & Cannon, P. M. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.019 · Cited by 27
Better living through chemistry: CRISPR/Cas engineered T cells for cancer immunotherapy
Wellhausen, N., Agarwal, S., Rommel, P. C., Gill, S. I., & June, C. H. (2021) · Current Opinion in Immunology · doi:10.1016/j.coi.2021.10.008 · Cited by 27
Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021
Ou, Z., Qiu, L., Rong, H., Li, B., Ren, S., Kuang, S., Lan, T., Lin, H., Li, Q., Wu, F., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.822004 · Cited by 24
Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma
Maldonado‐Pérez, N., Tristán‐Manzano, M., Justicia-Lirio, P., Martínez-Planes, E., Muñoz, P., Pavlovic, K., Cortijo-Gutierréz, M., Blanco-Benítez, C., Castellà, M., Juan, M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1011858 · Cited by 28
The potential for Treg-enhancing therapies in transplantation
Steiner, R., & Pilat, N. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac118 · Cited by 25
“These modifications would minimize the risk of side-effects such as alloreactivity resulting in GvHD, facilitating the development of ‘off the shelf’ CAR T-cell products [131, 132].”
Background
Metadata
- Authors
- Eyquem, J., Mansilla-Soto, J., Giavridis, T., van der Stegen, S. J. C., Hamieh, M., Cunanan, K. M., Odak, A., Gönen, M., & Sadelain, M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Sadelain, Michel
- ORCID
- Venue
- Nature
- Published
- 2017-02-22
- Volume
- 543
- Issue
- 7643
- Pages
- 113-117
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5558614
- OpenAlex
- W2589417329
- Semantic Scholar
- 47af46911569825ab86ac946a5c9cd502504aa3f
- Cited by
- 1,831
- References
- 33
- Citations by year
- 2026: 191 · 2025: 175 · 2024: 206 · 2023: 201 · 2022: 224 · 2021: 238 · 2020: 190 · 2019: 186 · 2018: 151 · 2017: 68
- FWCI
- 71.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- chimeric antigen receptor, CRISPR/Cas9 genome editing, CD19, chimeric antigen receptor T cells, T cell exhaustion, T cell differentiation, acute lymphoblastic leukemia, tumor rejection, targeted gene integration
- MeSH terms
- Gene Editing, Animals, Cell Differentiation, Disease Models, Animal, Gene Expression Regulation, Humans, Immunotherapy, Lymphocyte Activation, Male, Promoter Regions, Genetic, Receptors, Antigen, T-Cell, T-Lymphocytes, Receptors, Antigen, T-Cell, alpha-beta, Antigens, CD19, Mice, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genetic Loci, Translational Research, Biomedical, CRISPR-Cas Systems
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