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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It states that AAV6 donor templates with homology arms efficiently deliver donor DNA into sensitive primary immune cells such as HSPCs and T cells.
“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]
The Methods (AAV and Gene targeting; page not provided) describe an AAV6 donor with homologous TRAC sequences delivered to primary T cells. A results passage indexed under Abstract (page not provided) reports more than 40% CAR knock-in, supporting efficiency in T cells. The paper does not demonstrate this approach in HSPCs, so that extension is unsupported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTargeted integration of antigen receptor genes into defined genomic loci has potential advantages.
“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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Katti, A., Diaz, B. J., Caragine, C. M., Sanjana, N. E., & Dow, L. E. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00441-w · Cited by 440 · see citing works
Current understanding of osteoarthritis pathogenesis and relevant new approaches
Tong, L., Yu, H., Huang, X., Shen, J., Xiao, G., Chen, L., Wang, H., Xing, L., & Chen, D. (2022) · Bone Research · doi:10.1038/s41413-022-00226-9 · Cited by 437 · see citing works
“A particularly inspiring direction is the development of Cas9 as a therapeutic molecule for curing hereditary diseases.(160,161) Delivery tools for gene-editing molecules include adeno-associated viral vectors, lentiviral vectors, lipid nanoparticles, and other nonviral vectors.”
BackgroundInhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis
Mathewson, N. D., Ashenberg, O., Tirosh, I., Gritsch, S., Perez, E. M., Marx, S., Jerby‐Arnon, L., Chanoch-Myers, R., Hara, T., Richman, A. R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.022 · Cited by 402 · see citing works
“CD4 crRNA: (50-GGCAAGGCCACAATGAACCG-30) This paper; IDT N/A TRAC crRNA: (50-TCAGGGTTCTGGATATCTGT-30) (Eyquem et al., 2017); IDT N/A KLRB1 region#1 crRNA: (50-AATTAAAGCCACTTACCCCG-30) This paper; IDT N/A KLRB1 region#2 crRNA: (50-TTACCCCGAGGAAGAGATGA-30) This paper; IDT N/A”
Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion
Gumber, D., & Wang, L. D. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103941 · Cited by 409 · see citing works
RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges
Yu, A., Choi, Y. H., & Tu, M. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019554 · Cited by 405 · see citing works
“…of new therapies for the treatment of human diseases, including monogenetic disorders, infection, and cancer (Xue et al., 2014; Dever et al., 2016; Long et al., 2016; Nelson et al., 2016; Tabebordbar et al., 2016; Eyquem et al., 2017; Zhang et al., 2017; Georgiadis et al., 2018; Xu et al., 2019b).”
BackgroundAn “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies
Cooper, M. L., Choi, J., Staser, K. W., Ritchey, J., Devenport, J. M., Eckardt, K., Rettig, M. P., Wang, B., Eissenberg, L. G., Ghobadi, A., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0065-5 · Cited by 389 · see citing works
“Furthermore, insertion of the CAR directly into the TRAC locus, as recently reported [40, 41], or, potentially, the CD7 locus, would further mitigate the risk”
BackgroundEmerging Cellular Therapies for Cancer
Guedan, S., Ruella, M., & June, C. H. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041407 · Cited by 386 · see citing works
CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors
Jin, L., Tao, H., Karachi, A., Long, Y., Hou, A. Y., Meng, N., Dyson, K. A., Grippin, A., Deleyrolle, L. P., Zhang, W., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11869-4 · Cited by 388 · see citing works
Choi, J., Lim, J., Shin, M., Paek, S., & Choi, J.-W. (2020) · Nano Letters · doi:10.1021/acs.nanolett.0c04303 · Cited by 383 · see citing works
CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?
Wagner, J., Wickman, E., DeRenzo, C. C., & Gottschalk, S. M. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.09.015 · Cited by 383 · see citing works
“This resulted in consistent CAR expression, reduced baseline signaling, and improved antitumor activity compared to CD19-CAR T cells generated by viral transduction.(125) The clinical experience with CAR T cells generated with non-viral methods is so far limited,(78) and most ongoing studies are focused on targeting h…”
BackgroundCAR-T design: Elements and their synergistic function
Jayaraman, J., Mellody, M., Hou, A. J., Desai, R. P., Fung, A., Pham, A. H. T., Chen, Y. Y., & Zhao, W. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102931 · Cited by 389 · see citing works
“reduced tonic signaling and improved in vivo anti-tumor efficacy [35].”
BackgroundChimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy
Gong, Y., Klein Wolterink, R. G. J., Wang, J., Bos, G. M. J., & Germeraad, W. T. V. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01083-5 · Cited by 379 · see citing works
“TRAC-CAR-T outperformed both conventional retroviral transduced CAR T cells (RVCAR) as well as T cells with the CAR inserted in the β2M locus (β2M-CAR) in an in vivo mouse model, based on tumor eradication and expression of exhaustion markers, including PD1, TIM3 and LAG3 [40].”
BackgroundMethodInfluentialNon-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL
Zhang, J., Hu, Y., Yang, J., Li, W., Zhang, M., Wang, Q., Zhang, L., Wei, G., Tian, Y., Zhao, K., et al. (2022) · Nature · doi:10.1038/s41586-022-05140-y · Cited by 380 · see citing works
Seki, A., & Rutz, S. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171626 · Cited by 369 · see citing works
CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours
Larson, R. C., Kann, M. C., Bailey, S. R., Haradhvala, N. J., Llopis, P. D. L. M. M., Bouffard, A. A., Scarfò, I., Leick, M. B., Grauwet, K., Berger, T. R., et al. (2022) · Nature · doi:10.1038/s41586-022-04585-5 · Cited by 350 · see citing works
Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing
Dimitri, A. J., Herbst, F., & Fraietta, J. A. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01559-z · Cited by 370 · see citing works
Xu, X., Sun, Q., Liang, X., Chen, Z., Zhang, X., Zhou, X., Li, M., Tu, H., Liu, Y., Tu, S., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02664 · Cited by 351 · see citing works
“(48) reported that targeting a CD19-specific CAR coding sequence to the T-cell receptor (TCR) locus, placing it under the control of endogenous regulatory elements, not only led to uniform CAR expression in human peripheral blood Tcells but also promoted T-cell potency.”
BackgroundBlocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells
Kamiya, T., Seow, S. V., Wong, D., Robinson, M., & Campana, D. (2019) · Journal of Clinical Investigation · doi:10.1172/jci123955 · Cited by 337 · see citing works
“Downregulation of NKG2A might have also been achieved by using modern gene-editing methodologies based on mega-nucleases, TALEN, or CRISPR/Cas9, which have already been applied to genetically modify T lymphocytes (66–69).”
Principles and therapeutic applications of adaptive immunity
Chi, H., Pepper, M., & Thomas, P. G. (2024) · Cell · doi:10.1016/j.cell.2024.03.037 · Cited by 359 · see citing works
Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML
Haubner, S., Perna, F., Köhnke, T., Schmidt, C., Berman, S., Augsberger, C., Schnorfeil, F. M., Krupka, C., Lichtenegger, F. S., Liu, X., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0180-3 · Cited by 340 · see citing works
Self-citationSystematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells
Dong, M. B., Wang, G., Chow, R. D., Ye, L., Zhu, L., Dai, X., Park, J. J., Kim, H. R., Errami, Y., Guzman, C. D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.044 · Cited by 330 · see citing works
“CRISPR technology has provided a unique opportunity for direct manipulation of the T cell genome (Eyquem et al., 2017), and its scalability enabled genetic screens in T cells which to date have been performed in vitro (Henriksson et al.”
CRISPR/Cas9 for cancer research and therapy
Zhan, T., Rindtorff, N., Betge, J., Ebert, M., & Boutros, M. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.04.001 · Cited by 333 · see citing works
T cell receptor‐based cancer immunotherapy: Emerging efficacy and pathways of resistance
Chandran, S. S., & Klebanoff, C. A. (2019) · Immunological Reviews · doi:10.1111/imr.12772 · Cited by 325 · see citing works
Epigenetic regulation of T cell exhaustion
Belk, J. A., Dániel, B., & Satpathy, A. T. (2022) · Nature Immunology · doi:10.1038/s41590-022-01224-z · Cited by 334 · see citing works
Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy
Abou-el-Enein, M., Elsallab, M., Feldman, S. A., Fesnak, A. D., Heslop, H. E., Marks, P., Till, B. G., Bauer, G., & Savoldo, B. (2021) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-21-0084 · Cited by 321 · see citing works
“This strategy enables the disruption of the TCR by targeting the T-cell receptor alpha chain constant (TRAC) locus while simultaneously integrating the CAR construct into the genome (150).”
Rapid manufacturing of non-activated potent CAR T cells
Ghassemi, S., Durgin, J. S., Nuñez-Cruz, S., Patel, J., Leferovich, J. M., Pinzone, M. R., Shen, F., Cummins, K. D., Plesa, G., Cantu, V. A., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00842-6 · Cited by 311 · see citing works
CAR-T cell manufacturing: Major process parameters and next-generation strategies
Ceja, M. A., Khericha, M., Harris, C., Puig-Saus, C., & Chen, Y. (2024) · Journal of Experimental Medicine · doi:10.1084/jem.20230903 · Cited by 293 · see citing works
“This strategy commandeers the endogenous gene regulatory mechanisms that dynamically control TCR expression levels in response to T-cell activation states, with data suggesting that the resulting CAR-T cells may be more efficacious than virally integrated CAR-T cells (Eyquem et al., 2017).”
BackgroundCAR T cells: Continuation in a revolution of immunotherapy
Singh, A. K., & McGuirk, J. P. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30823-x · Cited by 303 · see citing works
Zhao, Y., Chen, J., Andreatta, M., Feng, B., Xie, Y., Wenes, M., Wang, Y., Gao, M., Hu, X., Romero, P. J., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-02060-8 · Cited by 303 · see citing works
“The CD19 hCAR comprised an scFv specific for human CD19 preceded by a CD8α leader peptide and followed by CD28 hinge–transmembrane–intracellular regions and a CD3ζ intracellular domain, as described in previous publications 34 .”
Recent Advances in CRISPR/Cas9 Delivery Strategies
Yip, B. H. (2020) · Biomolecules · doi:10.3390/biom10060839 · Cited by 303 · see citing works
Current status and perspectives of patient-derived xenograft models in cancer research
Lai, Y., Wei, X., Lin, S., Qin, L., Cheng, L., & Li, P. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0470-7 · Cited by 291 · see citing works
“The in vivo model with NSG mice was critical to demonstrate that targeting an anti-CD19 CAR to the TRAC locus with CRISPR/Cas9 enhances tumor rejection, a strategy averting antigen-stimulated differentiation and exhaustion [124].”
BackgroundChoi, B. D., Yu, X., Castaño, A. P., Darr, H., Henderson, D. B., Bouffard, A. A., Larson, R. C., Scarfò, I., Bailey, S. R., Gerhard, G. M., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0806-7 · Cited by 293 · see citing works
“An example of this is a prior report of a CD19 CAR construct delivered directly into the TRAC locus, which also placed the transgene under control of an endogenous promoter [7].”
BackgroundNon-viral precision T cell receptor replacement for personalized cell therapy
Foy, S. P., Jacoby, K., Bota, D. A., Hunter, T., Pan, Z., Stawiski, E. W., Ma, Y., Lu, W., Peng, S., Wang, C. L., et al. (2022) · Nature · doi:10.1038/s41586-022-05531-1 · Cited by 288 · see citing works
Gomes‐Silva, D., Mukherjee, M., Srinivasan, M., Krenciute, G., Dakhova, O., Zheng, Y., Cabral, J. M. S., Rooney, C. M., Orange, J. S., Brenner, M. K., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.015 · Cited by 287 · see citing works
CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity
Lazzarotto, C. R., Malinin, N. L., Li, Y., Zhang, R., Yang, Y., Lee, G., Cowley, E., He, Y., Lan, X., Jividen, K., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0555-7 · Cited by 283 · see citing works
The delivery challenge: fulfilling the promise of therapeutic genome editing
van Haasteren, J., Li, J., Scheideler, O. J., Murthy, N., & Schaffer, D. V. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0565-5 · Cited by 285 · see citing works
Next-generation stem cells — ushering in a new era of cell-based therapies
Kimbrel, E. A., & Lanza, R. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0064-x · Cited by 280 · see citing works
Nidhi, S., Anand, U., Olekšák, P., Tripathi, P., Lal, J. A., Thomas, G., Kuča, K., & Tripathi, V. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073327 · Cited by 294 · see citing works
Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape
DeSelm, C. J., Palomba, M. L., Yahalom, J., Hamieh, M., Eyquem, J., Rajasekhar, V. K., & Sadelain, M. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.09.008 · Cited by 275 · see citing works
“For TCR knockout, we used a gRNA that targets a sequence in the first exon of the constant chain of the TCRa gene (TRAC) that is required for the TCRa and b assembly and addressing it to the cellsurface, as described previously.(41) TRAIL was performed using synthetic modified gRNA kits (Synthego).”
MethodSelf-citationReversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide
Jan, M., Scarfò, I., Larson, R. C., Walker, A., Schmidts, A., Guirguis, A. A., Gasser, J. A., Slabicki, M. M., Bouffard, A. A., Castaño, A. P., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abb6295 · Cited by 270 · see citing works
“In future applications, if necessary, effects of degron or dimerization domains on receptor function could be mitigated by altering gene dosage or per-molecule signaling strength along established lines ( 34 , 36 , 42 , 43 ).”
Du, B., Qin, J., Lin, B., Zhang, J., Li, D., & Liu, M. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.03.019 · Cited by 281 · see citing works
Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors
Wang, Z., Li, N., Feng, K., Chen, M., Zhang, Y., Liu, Y., Yang, Q., Nie, J., Tang, N., Zhang, X., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00749-x · Cited by 267 · see citing works
Sheih, A., Voillet, V., Hanafi, L., DeBerg, H. A., Yajima, M., Hawkins, R. M., Gersuk, V. H., Riddell, S. R., Maloney, D. G., Wohlfahrt, M. E., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13880-1 · Cited by 264 · see citing works
Challenges and new technologies in adoptive cell therapy
Zhang, P., Zhang, G., & Wan, X. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01492-8 · Cited by 271 · see citing works
“TCR site destruction and CAR coding gene insertion by CRISPR/Cas9 has been reported to result in potentially universal CAR-T cells that effectively reduced tonic signaling and delayed exhaustion [172, 173].”
BackgroundMethodNanotechnology Strategies To Advance Outcomes in Clinical Cancer Care
Hartshorn, C. M., Bradbury, M. S., Lanza, G. M., Nel, A. E., Rao, J., Wang, A. Z., Wiesner, U. B., Yang, L. P. H., & Grodzinski, P. A. (2017) · ACS Nano · doi:10.1021/acsnano.7b05108 · Cited by 263 · see citing works
Wittsten, A. H., Yang, S., Park, M., Garcia, J. M., Alavi, J., Perry, N., Montgomery, G., Liu, B., & Roybal, K. T. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd8836 · Cited by 256 · see citing works
Boyiadzis, M. M., Dhodapkar, M. V., Brentjens, R. J., Kochenderfer, J. N., Neelapu, S. S., Maus, M. V., Porter, D. L., Maloney, D. G., Grupp, S. A., Mackall, C. L., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0460-5 · Cited by 249 · see citing works
Zhang, H., Qin, C., An, C., Zheng, X., Wen, S., Chen, W., Liu, X., Lv, Z., Yang, P., Xu, W., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01431-6 · Cited by 255 · see citing works
Watanabe, K., Kuramitsu, S., Posey, A. D., & June, C. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02486 · Cited by 245 · see citing works
“This difference in sustained lysis kinetics may be explained by CAR downmodulation after stimulation upon the antigen recognition, which can be ameliorated through TCR-based expression of CAR (41).”
BackgroundKuhn, N. F., Purdon, T. J., van Leeuwen, D. G., Lopez, A. V., Curran, K. J., Daniyan, A. F., & Brentjens, R. J. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.02.006 · Cited by 245 · see citing works
“by controlling CAR expression at a physiological level through targeted genomic integration of the CAR transgene (Eyquem et al., 2017), or by expressing a second transgene in addition to the CAR in T cells to enhance the antitumor efficacy of CAR T cells (Pegram et al.”
BackgroundGenetically engineered T cells for cancer immunotherapy
Li, D., Li, X., Zhou, W.-L., Huang, Y., Liang, X., Jiang, L., Yang, X., Sun, J., Li, Z., Han, W., et al. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0070-9 · Cited by 245 · see citing works
Cellular networks controlling T cell persistence in adoptive cell therapy
Chan, J. D., Lai, J., Slaney, C. Y., Kallies, A., Beavis, P. A., & Darcy, P. K. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00539-6 · Cited by 242 · see citing works
- 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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