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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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Straightforward Generation of Ultrapure Off-the-Shelf Allogeneic CAR-T Cells
Juillerat, A., Tkach, D., Yang, M., Boyne, A. R., Valton, J., Poirot, L., & Duchateau, P. N. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00678 · Cited by 19
“, 2017), or CRISPR/Cas9 (Eyquem et al., 2017; Georgiadis et al., 2018) can be used to inactivate TCRαβ at the molecular level.”
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“T cell exhaustion has been implicated as an important factor limiting the efficacy of CAR-T cells against cancer (Eyquem et al., 2017; Fraietta et al., 2018a; Fraietta et al., 2018b) and can be driven by excessive CAR signaling as a result of high antigen burden or tonic signaling induced by antigen-independent cluste…”
BackgroundHan, H., Sun, X., Guo, X., Wen, J., Zhao, X., & Zhou, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1552741 · Cited by 23
“Enhance the killing effect of CAR-T cells on solid tumors (Eyquem et al., 2017; Rupp et al., 2017), and recent studies have also demonstrated that the activation of tumor antigen expression by the CRISPR system controlled by focused ultrasound (FUS) can signi fi cantly improve the in fi ltration ef fi…”
Wen, P., Ai, Q., Fan, X., Gu, Z., 陈波, & Qian, H. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218257 · Cited by 20
Resistance and recurrence of malignancies after CAR-T cell therapy
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Clinical trials and promising preclinical applications of CRISPR/Cas gene editing
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CRISPR/Cas9-based genome editing for multimodal synergistic cancer nanotherapy
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“To insert the IL-12 transgene into the PDCD1 locus, we used CRISPR/Cas9 and AAV6-based knock-in systems, which have previously demonstrated robust and precise gene modifications in human T cells (38).”
MethodMohr, M., Damas, N. D., Gudmand‐Hoeyer, J., Zeeberg, K., Jędrzejczyk, D., Vlassis, A., Morera-Gómez, M., Pereira, S., Puš, U., Oliver-Almirall, A., et al. (2023) · ACS Synthetic Biology · doi:10.1021/acssynbio.2c00179 · Cited by 18
CAR-T cells for cancer immunotherapy
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Modeling Cancer in the CRISPR Era
Ventura, A., & Dow, L. E. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050455 · Cited by 18
“Two elegant studies (Drost et al. 2015, Matano et al. 2015) reported the sequential genome editing of wild-type human colon organoids to recapitulate the proposed Vogelgram of stepwise accumulated mutations in colorectal cancer (Fearon & Vogelstein 1990).”
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Antony, J. S., Haque, A. K. M. A., Lamsfus‐Calle, A., Daniel-Moreno, A., Mezger, M., & Kormann, M. (2018) · Advances in Cell and Gene Therapy · doi:10.1002/acg2.10 · Cited by 20
“receptors including PD-1, whereas the expression of CRISPR-based CAR T cells were physiologically controlled by the same genetic regulators that control the endogenous TCR expression.(7) In addition to the T-cell–directed immunotherapy against blood”
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New targets and technologies for CAR-T cells
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Immunotherapy perspectives in the new era of B-cell editing
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“To date, the occurrence of malignant transformation in CAR-T cells has not been found [114–116]; however, some techniques have been used to reduce this risk, such CRISPR-mediated gene integration, which prevents random DNA-insertion [17, 18, 21, 115], and engendering of CAR-T cells with capability of apoptosis or remo…”
BackgroundMethodNovel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice
Chuntova, P., Hou, Y., Naka, R., Yamamichi, A., Chen, T., Goretsky, Y. E., Hatae, R., Nejo, T., Kohanbash, G., Mende, A., et al. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab182 · Cited by 20
Toxicities associated with immunotherapies for hematologic malignancies
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Immunotherapy for the Treatment of Acute Lymphoblastic Leukemia
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Lung cancer immunotherapy in 2025: where we stand and what comes next?
Han, J., Yang, Z., & Hai, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1728163 · Cited by 17
“…the cancer-testis antigen NY-ESO-1, while simultaneously disrupting the PDCD1 (encoding PD-1) and TRAC (T-cell receptor a constant) genes (149, 150) The deletion of endogenous TCR prevents mispairing and autoimmunity, while the knockout of PD-1 shields the engineered cells from checkpoint…”
The progress of CAR-T therapy in cancer and beyond
Huang, Y., Li, L., Liu, W., Tang, T., & Chen, L. (2020) · STEMedicine · doi:10.37175/stemedicine.v1i3.47 · Cited by 17
Mechanogenetics for cellular engineering and cancer immunotherapy
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Schultz, L. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01985 · Cited by 18
“Targeted CAR insertion to the T-cell receptor α constant (TRAC) locus using CRISPR/Cas9 has been explored as a method to avert tonic signaling and defer effector-T cell differentiation and exhaustion (27).”
MethodGenome editing of immune cells using CRISPR/Cas9
Kim, S., Hupperetz, C., Kim, C. H., & Kim, C. H. (2021) · BMB Reports · doi:10.5483/bmbrep.2021.54.1.245 · Cited by 21
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Chimeric Antigen Receptor T-Cell Therapy: What We Expect Soon
Martino, M., Naso, V., Loteta, B., Canale, F. A., Pugliese, M., Alati, C., Musuraca, G., Nappi, D., Gaimari, A., Nicolini, F., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113332 · Cited by 17
“The investigation of adding a suicide gene that monoclonal antibodies may trigger, such as rituximab or cetuximab, or by using the CRISPR/Cas9 genome editing technology to clone a specific CAR construct to the T-cell receptor α constant (TRAC) locus resulting in uniform CAR expression and enhanced T-cell potency, need…”
BackgroundActivation of cancer immunotherapy by nanomedicine
Wang, L., Xu, H., Weng, L., Sun, J., Jin, Y. H., & Xiao, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1041073 · Cited by 18
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“In preclinical animal models of leukemia, this approach resulted in enhanced T cell therapeutic potency and less tonic CAR signaling, thereby delaying T cell differentiation and exhaustion, and maintaining longer sustainability with very limited off-target events [78, 79].”
Next-generation CRISPR technology for genome, epigenome and mitochondrial editing
Lau, C., Liang, Q., & Zhu, H. (2024) · Transgenic Research · doi:10.1007/s11248-024-00404-x · Cited by 19
“Targeting a CAR transgene to the T-cell receptor α constant (TRAC) locus also can enhance anti-tumor activity of CAR-T cells (Eyquem et al. 2017).”
Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles
Degtev, D., Bravo, J. P. K., Emmanouilidi, A., Zdravković, A., Choong, O. K., Touza, J. L., Selfjord, N., Weisheit, I., Francescatto, M., Akçakaya, P., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53418-8 · Cited by 19
Reprint of: Building a Safer and Faster CAR: Seatbelts, Airbags, and CRISPR
Perales, M., Kebriaei, P., Kean, L. S., & Sadelain, M. (2018) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2017.12.789 · Cited by 17
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Chimeric Antigen Receptor T Cells: Extending Translation from Liquid to Solid Tumors
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CART manufacturing process and reasons for academy-pharma collaboration
Egri, N., de Landazuri, I. O., Bartolomé, C. S., Ortega, J. R., Español‐Rego, M., & Juan, M. (2019) · Immunology Letters · doi:10.1016/j.imlet.2019.10.014 · Cited by 18
Targeted multi-epitope switching enables straightforward positive/negative selection of CAR T cells
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Titratable Pharmacological Regulation of CAR T Cells Using Zinc Finger-Based Transcription Factors
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Allogeneic Chimeric Antigen Receptor Therapy in Lymphoma
Khurana, A., & Lin, Y. (2022) · Current Treatment Options in Oncology · doi:10.1007/s11864-021-00920-6 · Cited by 17
Personal tumor antigens in blood malignancies: genomics-directed identification and targeting
Penter, L., & Wu, C. J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129209 · Cited by 17
“Likewise, the development of CRISPR/Cas9 gene editing (173), the discovery efforts with genome-wide screens (174), and developments in the area of spatial tissue-based characterization (175) will have important implications for the delivery of novel targets and subsequent engineering of immune responses.”
BackgroundShy, B. R., Vykunta, V. S., Ha, A. S., Roth, T. L., Talbot, A., Nguyen, D. N., Chen, Y. Y., Blaeschke, F., Vedova, S., Mamedov, M. R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.02.458799 · Cited by 18
Self-citationHPV-driven cancers: a looming threat and the potential of CRISPR/Cas9 for targeted therapy
Kermanshahi, A. Z., Ebrahimi, F., Taherpoor, A., Eslami, N., & Baghi, H. B. (2025) · Virology Journal · doi:10.1186/s12985-025-02783-x · Cited by 18
“Additionally, hematological malignancies such as leukemia have utilized CRISPR to target CD19 and CD22 genes, improving CAR-T cell therapy effectiveness [40].”
Prime assembly with linear DNA donors enables large genomic insertions
Liu, B., Petti, A., Zhou, X., Cheng, H., Gao, J., Yee, M., Qiao, Y., Zhang, Y., Zhou, L. M., Wolfe, S. A., et al. (2026) · Nature · doi:10.1038/s41586-026-10460-4 · Cited by 15
“Lastly, we tested whether a CD19-specific chimeric antigen receptor (CAR) gene could be efficiently inserted into the TRAC locus in HEK293T cells 41 .”
Bernard, G., & Evgin, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1664403 · Cited by 14
Taking regulatory T-cell therapy one step further
Sicard, A., Boardman, D. A., & Levings, M. K. (2018) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000566 · Cited by 16
A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo
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Off-the-Shelf Chimeric Antigen Receptor T Cells
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‘Off-the-Shelf’ Immunotherapy: Manufacture of CD8+ T Cells Derived from Hematopoietic Stem Cells
Boyd, N. R., Cartledge, K., Cao, H., Evtimov, V. J., Pupovac, A., Trounson, A. O., & Boyd, R. L. (2021) · Cells · doi:10.3390/cells10102631 · Cited by 16
“Both of these health risks could be addressed by replacing the TCRαβ with a CAR [58,59], but these cells would then lack the advantages of a TCR specificity repertoire.”
BackgroundRecent Advances in CAR T-Cell Therapy for Patients with Chronic Lymphocytic Leukemia
Heyman, B. M., Tzachanis, D., & Kipps, T. J. (2022) · Cancers · doi:10.3390/cancers14071715 · Cited by 17
“Furthermore, directing a CD19-specific CAR specifically to the T-cell receptor α constant (TRAC) locus results in enhanced T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in preclinical leukemia models [76] (Figure 2).”
BackgroundManufacturing next-generation regulatory T-cell therapies
MacDonald, K. N., Salim, K., & Levings, M. K. (2022) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2022.102822 · Cited by 16
Peptide Vaccines in Melanoma: Chemical Approaches towards Improved Immunotherapeutic Efficacy
Biri‐Kovács, B., Bánóczi, Z., Tummalapally, A., & Szabó, I. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020452 · Cited by 16
“and homologous recombination after gene editing [46].”
Correcting inborn errors of immunity: From viral mediated gene addition to gene editing
Castiello, M. C., Ferrari, S., & VILLA, A. M. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101731 · Cited by 16
Little, S. R., Leung, Z., Quach, A. B. V., Hirukawa, A., Gholizadeh, F., Hajiaghayi, M., Darlington, P. J., & Shih, S. C. C. (2023) · Advanced Materials Technologies · doi:10.1002/admt.202300719 · Cited by 16
Kruglova, N. A., & Shepelev, M. V. (2024) · Biomedicines · doi:10.3390/biomedicines12010119 · Cited by 18
“The first data were obtained in the study by Eyquem et al., who inserted the CAR T gene into the TRAC locus and compared this approach to transduction [26].”
BackgroundMethodResultInfluentialBanda, A., Impomeni, O., Singh, A., Baloch, A. R., Hu, W., & Jaijyan, D. K. (2024) · Vaccines · doi:10.3390/vaccines12060636 · Cited by 16
“Interestingly, the CRISPR-Cas system has also been used to insert CAR cassettes at specific locations in the genome [205].”
MethodPorreca, I., Blassberg, R. A., Harbottle, J. A., Joubert, B. C., Mielczarek, O., Stombaugh, J., Hemphill, K., Sumner, J., Pazeraitis, D., Touza, J. L., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.06.033 · Cited by 16
“Information regarding gRNAs utilized with SpCas9 for optimal indels formation 45,47,48 are reported in Table S14.”
InfluentialGene editing in T cell therapy
Zhang, Y., Mu, W., & Wang, H. (2017) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2017.09.002 · Cited by 18
Karadimitris, A., Fiol, C. R., & Guerra, J. C. (2019) · HemaSphere · doi:10.1097/hs9.0000000000000220 · Cited by 15
RETRACTED ARTICLE: Elucidation of CRISPR-Cas9 application in novel cellular immunotherapy
Quazi, S. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07147-0 · Cited by 22
RetractedKrackhardt, A. M., Anliker, B., Hildebrandt, M., Bachmann, M. P., Eichmüller, S. B., Nettelbeck, D. M., Renner, M., Uharek, L., Willimsky, G., Schmitt, M. W., et al. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2119-y · Cited by 18
“Nevertheless, developments such as non-viral genetic transfer by RNA [34], the use of transposons [35–37], or of novel gene-editing technologies [38] may further reduce risks associated with viral gene transfer.”
BackgroundCurrent Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas
Poggio, T., Duyster, J., & Illert, A. L. (2018) · Cancers · doi:10.3390/cancers10090339 · Cited by 16
“In preclinical models, gene editing approaches, such as CRISPR/Cas9-mediated editing and transcription activator-like effector nucleases (TALENs), have been employed to target novel antigens and increase the effectiveness of CAR-T cells [95,96].”
MethodRegulatory Cell Therapy in Organ Transplantation: Achievements and Open Questions
Fortunato, M., Morali, K., Passeri, L., & Gregori, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.641596 · Cited by 16
“These can be overcome by the development of CRISPR/Cas9 technology, which will further optimize the cell product (56, 57).”
BackgroundTargeted, programmable, and precise tandem duplication in the mammalian genomePreprint
Jiao, Y., Li, M., He, X., Wang, Y., Song, J., Hu, Y. F., Li, L., Zhou, L., Jiang, L., Qu, J., et al. (2023) · Genome Research · doi:10.1101/gr.277261.122 · Cited by 16
“…especially the ones based on the CRISPR-Cas9 system, are readily reprogram-mable for genome manipulating purpose, providing powerful tools for basic biomedical research and clinical translation (Cong et al. 2013; Nelson et al. 2016; Eyquem et al. 2017; Rees and Liu 2018; Schene et al. 2020).”
In vivo production of CAR T cell: Opportunities and challenges
Song, Z., Zhou, Y., Wang, B., Geng, Y., Tang, G., Wang, Y., & Yang, J. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101612 · Cited by 17
“94 MacLeod et al produced allogeneic CAR T cells by target-inserting a CAR transgene into the T-cell receptor locus using an AAV donor template and endonuclease, making it possible for patients with advanced disease or insufficient CAR T cells to receive CAR T cell therapy.”
Clinical development of allogeneic chimeric antigen receptor αβ-T cells
Georgiadis, C., Preece, R., & Qasim, W. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.040 · Cited by 17
“77,80,81 A similar strategy has used CRISPR-Cas12a and chimeric RNA-DNA guides in combination with AAV template delivery CAR and non-polymor-phic HLA.”
Mazziotta, F., Martin, L. E., Egan, D. N., Bar, M., Kinsella, S. M., Paulson, K. G., Voillet, V., Lahman, M. C., Hunter, D. S., Schmitt, T. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60394-0 · Cited by 16
“In solid tumors and lymphomas, reduced persistence generally correlates with T-cell exhaustion 16,19 , characterized by markers like PD-1, CTLA-4, Tim3, LAG-3, BTLA and/or TIGIT 20 .”
A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T cell therapy
Zhang, Z., Ho, Y.-J., Fang, X., Kim, M., Li, M., Luan, W., Hinterleitner, C., Haubner, S., Kogel, F., Pratt, E. C., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.002 · Cited by 15
Self-citationRobust In Vitro Pharmacology of Tmod, a Synthetic Dual-Signal Integrator for Cancer Cell Therapy
Manry, D., Bolanos, K., DiAndreth, B., Mock, J., & Kamb, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.826747 · Cited by 15
Barreira, M., Kerridge, C., Jorda, S., Olofsson, D., Neumann, A., Horton, H., & Smith‐Moore, S. (2022) · Gene Therapy · doi:10.1038/s41434-022-00343-4 · Cited by 15
Engineering off-the-shelf universal CAR T cells: A silver lining in the cloud
Muthuvel, M., Srinivasan, H., Louis, L., & Martin, S. (2022) · Cytokine · doi:10.1016/j.cyto.2022.155920 · Cited by 16
DLK1 ‐directed chimeric antigen receptor T‐cell therapy for hepatocellular carcinoma
Zhai, Y., He, K., Huang, L., Shang, X., Wang, G., Yuan, G., & Han, Z. (2022) · Liver International · doi:10.1111/liv.15411 · Cited by 15
Lu, Q., Yang, D., Li, H., Zhu, Z., Zhang, Z., Chen, Y., Yang, N., Li, J., Wang, Z., Niu, T., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216660 · Cited by 15
Overcoming the challenges of primary resistance and relapse after CAR-T cell therapy
Dreyzin, A., Rankin, A. W., Luciani, K., Gavrilova, T., & Shah, N. N. (2024) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2024.2349738 · Cited by 17
“Other strategies aimed at construct optimization to improve persistence include, for example, engineering approaches to alter the interaction between CD28 and Lck [114,115] and integration of CAR DNA into the TRAC locus to allow for downregulation of CAR expression upon antigen exposure [163].”
BackgroundRecent advances and progress in immunotherapy of solid cancers
Kumar, A., Emdad, L., Das, S. K., & Fisher, P. B. (2024) · Advances in cancer research · doi:10.1016/bs.acr.2024.05.004 · Cited by 15
Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer
Du, W., Noyan, F., McCallion, O., Drosdek, V., Kath, J., Glaser, V., Fuster-García, C., Yang, M.-X., Stein, M., Franke, C., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.01.045 · Cited by 12
“30 Miniaturization of the CAR transgene has been proposed by inserting truncated CD3 z -de fi cient second-generation CARs into the CD3 z gene in Tconvs and Tregs.”
Expanding the horizon of CAR T cell therapy: from cancer treatment to autoimmune diseases and beyond
Yang, Z., Ha, B., Wu, Q., Ren, F., Yin, Z., & Zhang, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1544532 · Cited by 18
Prevention and treatment of relapse after stem cell transplantation by cellular therapies
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An Overview on Diffuse Large B-Cell Lymphoma Models: Towards a Functional Genomics Approach
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“However, CRISPR-Cas9 has shown promising results in preclinical studies involving immunotherapy with CAR T-cells, indicating its therapeutic potential [52].”
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“Expression of this CAR follows endogenous regulation by the regulatory elements of the TCR alpha locus and was associated with reduced exhaustion and increased efficacy [73].”
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RetractedImmunotherapy of sarcomas with modified T cells
Mahalingam, P., Julve, M., Huang, P. H., Furness, A. J. S., Pollack, S. M., & Jones, R. L. (2022) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000843 · Cited by 15
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“a CD19-specific CAR into the TCR α constant (TRAC) locus resulted in uniform expression and also enhanced T cell potency compared to conventionally generated CAR T cells, showing promising prospects for gene-edited CAR T cell products [68].”
BackgroundCRISPR/Cas9 genome engineering in hematopoietic cells
Sürün, D., von Melchner, H., & Schnütgen, F. (2018) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2018.08.001 · Cited by 16
NextGen cell-based immunotherapies in cancer and other immune disorders
Azimi, C. S., Tang, Q., Roybal, K. T., & Bluestone, J. A. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2019.03.007 · Cited by 13
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Kararoudi, M. N., Likhite, S. B., Elmas, E., Yamamoto, K., Schwartz, M., Sorathia, K., Pereira, M. D. S. F., Devin, R. D., Lyberger, J. M., Behbehani, G. K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.17.435886 · Cited by 15
Myeloid cells meet CD8+ T cell exhaustion in cancer: What, why and how
Zhai, Y., Liang, X., & Deng, M. (2024) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2024.06.04 · Cited by 14
Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond
Li, Y., Liu, Y., & Lin, X. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01304-8 · Cited by 17
Li, Z., Yang, F., Wu, X., Wu, X., Li, S., & Wang, M. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217928 · Cited by 14
BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells
Hu, T., Zhu, Z., Ying, L., Wizzard, S., Hoar, J., Shinde, S. S., Yihunie, K. D., Yao, C., & Wu, T. (2026) · Nature Immunology · doi:10.1038/s41590-025-02388-0 · Cited by 16
Quantitative contributions of TNF receptor superfamily members to CD8+ T‐cell responses
Nguyen, J., Pettmann, J., Krüger, P., & Dushek, O. (2021) · Molecular Systems Biology · doi:10.15252/msb.202110560 · Cited by 14
“…4-1BB co-stimulatory domains directly into a CAR might limit its effectiveness, as CARs are also known to be downregulated upon triggering (Eyquem et al , 2017; Trendel et al , 2021), and we have shown that co-stimulatory receptors that are downregulated along-side the TCR (such as CD27)…”
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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