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T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial
Open accessAbstract
Background Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells. Methods This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1-30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3 + 3 design to establish the maximum tolerated dose, patients received either 1 × 10(6) CAR-transduced T cells per kg (dose 1), 3 × 10(6) CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696. Findings Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defined as 1 × 10(6) CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). Interpretation CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. Funding National Institutes of Health Intramural funds and St Baldrick's Foundation.
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“All approved CAR T-cell products are second-generation CARs that incorporate CD28 or CD137 (4-1BB) co-stimulatory signals, which are essential for eliciting effector and memory cell expansion and persistence and a clinically relevant immune response (9-15).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [14]
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“Further, most clinical protocols, and all the commercially approved therapies, have relied on viral vectors to deliver CAR transgenes into T cells (9-14,24-26).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [14]
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“First, most CAR T cell trials to date have used autologous peripheral blood and apheresis as the main cell sources for manufacturing (9-18,21,22).”
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Citations
Cites
C-reactive protein: a critical update
Pepys, M. B., & Hirschfield, G. M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18921 · Cited by 4,694
Revised response criteria for malignant lymphoma.
Cheson, B. D., Pfistner, B., Juweid, M., Gascoyne, R., Specht, L., Horning, S., Coiffier, B., Fisher, R. I., Hagenbeek, A., Zucca, E., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.09.2403 · Cited by 4,537
Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103849 · Cited by 3,565
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
C-reactive protein: a critical update
Pepys, M. B., & Hirschfield, G. M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318921 · Cited by 3,436
Current concepts in the diagnosis and management of cytokine release syndrome.
Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., Grupp, S. A., & Mackall, C. L. (2014) · Blood · doi:10.1182/blood-2014-05-552729 · Cited by 2,806
Self-citationMorgan, R. A., Yang, J. C.-H., Kitano, M., Dudley, M. E., Laurençot, C. M., & Rosenberg, S. A. (2010) · Molecular Therapy · doi:10.1038/mt.2010.24 · Cited by 2,564
Self-citationEfficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
Davila, M. L., Rivière, I., Wang, X., Bartido, S. M., Park, J. H., Curran, K. J., Chung, S. S., Stefanski, J., Bórquez-Ojeda, O., Olszewska, M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008226 · Cited by 2,514
Kalos, M. D., Levine, B. L., Porter, D. L., Katz, S. I., Grupp, S. A., Bagg, A., & June, C. H. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002842 · Cited by 2,417
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
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Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., Maus, M. V., Park, J. H., Mead, E., Pavletic, S., et al. (2019) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2018.12.758 · Cited by 3,675
Self-citationZhang, Y., & Zhang, Z. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0488-6 · Cited by 2,906
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709919 · Cited by 2,688
Adoptive cell transfer as personalized immunotherapy for human cancer
Rosenberg, S. A., & Restifo, N. P. (2015) · Science · doi:10.1126/science.aaa4967 · Cited by 2,545
Self-citationChimeric antigen receptor T-cell therapy—assessment and management of toxicities
Neelapu, S. S., Tummala, S., Kebriaei, P., Wierda, W., Gutierrez, C., Locke, F. L., Komanduri, K. V., Lin, Y., Jain, N., Daver, N., et al. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.148 · Cited by 2,438
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June, C. H., & Sadelain, M. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1706169 · Cited by 2,411
Locke, F. L., Ghobadi, A., Jacobson, C. A., Miklos, D. B., Lekakis, L. J., Oluwole, O. O., Lin, Y., Braunschweig, I., Hill, B. T., Timmerman, J. M., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30864-7 · Cited by 2,286
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia
Kantarjian, H. M., Stein, A. S., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J., Wei, A. H., Dombret, H., Foà, R., Bassan, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609783 · Cited by 2,204
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Turtle, C. J., Hanafi, L.-A., Berger, C., Gooley, T. A., Cherian, S., Hudecek, M., Sommermeyer, D., Melville, K., Pender, B., Budiarto, T. M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85309 · Cited by 2,112
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
Self-citationFraietta, J. A., Lacey, S. F., Orlando, E. J., Pruteanu-Malinici, I., Gohil, M., Lundh, S., Boesteanu, A. C., Wang, Y., O’Connor, R. S., Hwang, W.-T., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0010-1 · Cited by 1,785
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Self-citationPorter, D. L., Hwang, W.-T., Frey, N. V., Lacey, S. F., Shaw, P. A., Loren, A. W., Bagg, A., Marcucci, K. T., Shen, A., Gonzalez, V., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac5415 · Cited by 1,729
Shimabukuro‐Vornhagen, A., Gödel, P., Subklewe, M. S., Stemmler, H., Schlößer, H., Schlaak, M. S., Kochanek, M., Böll, B., & von Bergwelt‐Baildon, M. S. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0343-9 · Cited by 1,712
Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia
Kantarjian, H. M., DeAngelo, D. J., Stelljes, M., Martinelli, G., Liedtke, M., Stock, W., Gökbuget, N., O'Brien, S. M., Wang, K., Wang, T., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1509277 · Cited by 1,444
Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410
Toxicities of chimeric antigen receptor T cells: recognition and management
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Self-citationLong-term outcomes following CAR T cell therapy: what we know so far
Cappell, K. M., & Kochenderfer, J. N. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00754-1 · Cited by 1,503
Self-citationA review of cancer immunotherapy toxicity
Kennedy, L. B., & Salama, A. K. S. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21596 · Cited by 1,396
Fry, T. J., Shah, N. N., Orentas, R. J., Stetler‐Stevenson, M., Yuan, C. M., Ramakrishna, S., Wolters, P. L., Martin, S. C., Delbrook, C., Yates, B., et al. (2017) · Nature Medicine · doi:10.1038/nm.4441 · Cited by 1,363
Self-citationAcute lymphoblastic leukemia: a comprehensive review and 2017 update
Terwilliger, T., & Abdul‐Hay, M. (2017) · Blood Cancer Journal · doi:10.1038/bcj.2017.53 · Cited by 1,353
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Giavridis, T., van der Stegen, S. J. C., Eyquem, J., Hamieh, M., Piersigilli, A., & Sadelain, M. (2018) · Nature Medicine · doi:10.1038/s41591-018-0041-7 · Cited by 1,272
Kawalekar, O. U., O’Connor, R. S., Fraietta, J. A., Guo, L., McGettigan, S. E., Posey, A. D., Patel, P. R., Guedan, S., Scholler, J., Keith, B., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.021 · Cited by 1,267
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The future of cancer treatment: immunomodulation, CARs and combination immunotherapy
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Hay, K. A., Hanafi, L.-A., Li, D., Gust, J., Liles, W. C., Wurfel, M. M., López, J. A., Chen, J., Chung, D., Harju-Baker, S., et al. (2017) · Blood · doi:10.1182/blood-2017-06-793141 · Cited by 1,156
Gardner, R., Finney, O. C., Annesley, C., Brakke, H., Summers, C. N., Leger, K. J., Bleakley, M., Brown, C., Mgebroff, S., Kelly‐Spratt, K. S., et al. (2017) · Blood · doi:10.1182/blood-2017-02-769208 · Cited by 1,142
Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy
Morris, E. C., Neelapu, S. S., Giavridis, T., & Sadelain, M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00547-6 · Cited by 1,187
Teachey, D. T., Lacey, S. F., Shaw, P. A., Melenhorst, J. J., Maude, S. L., Frey, N., Pequignot, E., Gonzalez, V. E., Chen, F., Finklestein, J., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0040 · Cited by 1,102
Engineered T cells: the promise and challenges of cancer immunotherapy
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Turtle, C. J., Hanafi, L.-A., Berger, C., Hudecek, M., Pender, B., Robinson, E., Hawkins, R., Chaney, C., Cherian, S., Chen, X., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf8621 · Cited by 1,016
Mechanisms of resistance to CAR T cell therapy
Shah, N. N., & Fry, T. J. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0184-6 · Cited by 999
Self-citationSantomasso, B. D., Park, J. H., Salloum, D., Riviere, I., Flynn, J., Mead, E., Halton, E., Wang, X., Senechal, B., Purdon, T., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1319 · Cited by 942
Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium
Falzone, L., Salomone, S., & Libra, M. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01300 · Cited by 959
Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management
Brudno, J. N., & Kochenderfer, J. N. (2018) · Blood Reviews · doi:10.1016/j.blre.2018.11.002 · Cited by 935
Self-citationMolecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells
Qasim, W., Zhan, H., Samarasinghe, S., Adams, S., Amrolia, P., Stafford, S., Butler, K., Rivat, C., Wright, G., Somana, K., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaj2013 · Cited by 902
Daillère, R., Vétizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., Duong, C. P. M., Flament, C., Lepage, P., Roberti, M. P., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.009 · Cited by 897
Toxicity and management in CAR T-cell therapy
Bonifant, C. L., Jackson, H. J., Brentjens, R. J., & Curran, K. J. (2016) · Molecular Therapy — Oncolytics · doi:10.1038/mto.2016.11 · Cited by 911
Therapeutic T cell engineering
Sadelain, M., Rivière, I., & Riddell, S. R. (2017) · Nature · doi:10.1038/nature22395 · Cited by 906
Le, R. Q., Li, L., Yuan, W., Shord, S. S., Nie, L., Habtemariam, B. A., Przepiorka, D., Farrell, A. T., & Pazdur, R. (2018) · The Oncologist · doi:10.1634/theoncologist.2018-0028 · Cited by 887
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 888
Rapoport, A. P., Stadtmauer, E. A., Binder-Scholl, G. K., Goloubeva, O. G., Vogl, D. T., Lacey, S. F., Badros, A. Z., Garfall, A. L., Weiss, B. M., Finklestein, J. M., et al. (2015) · Nature Medicine · doi:10.1038/nm.3910 · Cited by 884
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Ahmed, N. M., Brawley, V. S., Hegde, M. G., Bielamowicz, K., Kalra, M., Landi, D. B., Robertson, C. S., Gray, T., Diouf, O., Wakefield, A., et al. (2017) · JAMA Oncology · doi:10.1001/jamaoncol.2017.0184 · Cited by 884
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
Reprogramming human T cell function and specificity with non-viral genome targeting
Roth, T. L., Puig-Saus, C., Yu, R., Shifrut, E., Carnevale, J., Li, P. J., Hiatt, J., Saco, J., Krystofinski, P., Li, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0326-5 · Cited by 839
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Majzner, R. G., Ramakrishna, S., Yeom, K. W., Patel, S., Chinnasamy, H., Schultz, L. M., Richards, R. M., Jiang, L., Barsan, V. V., Mancusi, R. A., et al. (2022) · Nature · doi:10.1038/s41586-022-04489-4 · Cited by 862
Self-citationLiu, E., Tong, Y., Dotti, G., Shaim, H., Savoldo, B., Mukherjee, M., Orange, J. S., Wan, X., Lu, X. Y., Reynolds, A., et al. (2017) · Leukemia · doi:10.1038/leu.2017.226 · Cited by 843
Sun, X., Zhang, Y., Li, J., Park, K. S., Han, K., Zhou, X., Xu, Y., Nam, J., Xu, J., Shi, X., et al. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00962-9 · Cited by 808
Brudno, J. N., Marić, I., Hartman, S. D., Rose, J. J., Wang, M., Lam, N., Stetler‐Stevenson, M., Salem, D., Yuan, C. M., Pavletic, S. Z., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.77.8084 · Cited by 792
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Ali, S. A., Shi, V., Marić, I., Wang, M. L., Stroncek, D. F., Rose, J. J., Brudno, J. N., Stetler‐Stevenson, M., Feldman, S. A., Hansen, B. G., et al. (2016) · Blood · doi:10.1182/blood-2016-04-711903 · Cited by 776
Self-citationGardner, R., Wu, D., Cherian, S., Fang, M., Hanafi, L., Finney, O. C., Smithers, H. M., Jensen, M. C., Riddell, S. R., Maloney, D. G., et al. (2016) · Blood · doi:10.1182/blood-2015-08-665547 · Cited by 751
TRUCKs: the fourth generation of CARs
Chmielewski, M. M., & Abken, H. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1046430 · Cited by 783
Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease
Ellebrecht, C. T., Bhoj, V. G., Nace, A., Choi, E. J., Mao, X., Cho, M. J., Zenzo, G. D., Lanzavecchia, A., Seykora, J. T., Cotsarelis, G., et al. (2016) · Science · doi:10.1126/science.aaf6756 · Cited by 751
CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia
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Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms
Huang, X., Hussain, B., & Chang, J. (2020) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13569 · Cited by 759
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Majzner, R. G., Theruvath, J. L., Nellan, A., Heitzeneder, S., Cui, Y., Mount, C. W., Rietberg, S. P., Linde, M. H., Xu, P., Rota, C., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0432 · Cited by 681
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Self-citationTurtle, C. J., Hay, K. A., Hanafi, L., Li, D., Cherian, S., Chen, X., Wood, B. L., Lozanski, A., Byrd, J. C., Heimfeld, S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.72.8519 · Cited by 664
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Self-citationIonizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering
Billingsley, M. M., Singh, N., Ravikumar, P., Zhang, R., June, C. H., & Mitchell, M. J. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b04246 · Cited by 636
Ghorashian, S., Kramer, A. M., Onuoha, S. C., Wright, G., Bartram, J. L., Richardson, R., Albon, S. J., Castro, F., Popova, B., Villanueva, K., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0549-5 · Cited by 642
T memory stem cells in health and disease
Gattinoni, L., Speiser, D. E., Lichterfeld, M. D., & Bonini, C. (2017) · Nature Medicine · doi:10.1038/nm.4241 · Cited by 648
Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling
Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Dániel, B., Klysz, D. D., et al. (2021) · Science · doi:10.1126/science.aba1786 · Cited by 653
Self-citationKagoya, Y., Tanaka, S., Guo, T., Anczurowski, M., Wang, C.-H., Saso, K., Butler, M. O., Minden, M. D., & Hirano, N. (2018) · Nature Medicine · doi:10.1038/nm.4478 · Cited by 654
Jackson, H. J., Rafiq, S., & Brentjens, R. J. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.36 · Cited by 613
Spiegel, J. Y., Patel, S., Muffly, L. S., Hossain, N. M., Oak, J. S., Baird, J. H., Frank, M. J., Shiraz, P., Sahaf, B., Craig, J. K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01436-0 · Cited by 640
Self-citationZah, E., Lin, M.-Y., Silva-Benedict, A., Jensen, M. C., & Chen, Y. Y. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0231 · Cited by 615
Metabolic barriers to cancer immunotherapy
DePeaux, K., & Delgoffe, G. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00541-y · Cited by 626
Poirot, L., Philip, B., Schiffer-Mannioui, C., Le Clerre, D., Chion-Sotinel, I., Derniame, S., Potrel, P., Bas, C., Lemaire, L., Galetto, R., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3321 · Cited by 605
Brudno, J. N., Somerville, R. P. T., Shi, V. J., Rose, J. J., Halverson, D. C., Fowler, D. H., Gea‐Banacloche, J., Pavletic, S. Z., Hickstein, D. D., Lu, T., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.5929 · Cited by 605
Self-citationCombination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors
Grosser, R., Cherkassky, L., Chintala, N., & Adusumilli, P. S. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.006 · Cited by 603
Tuning the Antigen Density Requirement for CAR T-cell Activity
Majzner, R. G., Rietberg, S. P., Sotillo, E., Dong, R., Vachharajani, V. T., Labanieh, L., Myklebust, J. H., Kadapakkam, M., Weber, E. W., Tousley, A. M., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0945 · Cited by 596
Self-citationInfectious complications of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy
Hill, J. A., Li, D., Hay, K. A., Green, M. L., Cherian, S., Chen, X., Riddell, S. R., Maloney, D. G., Boeckh, M., & Turtle, C. J. (2017) · Blood · doi:10.1182/blood-2017-07-793760 · Cited by 588
Immunotherapy for osteosarcoma: Fundamental mechanism, rationale, and recent breakthroughs
Chen, C., Xie, L., Ren, T., Huang, Y., Xu, J. H., & Guo, W. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.12.024 · Cited by 582
Kochenderfer, J. N., Somerville, R. P. T., Lu, T., Shi, V., Bot, A., Rossi, J., Xue, A., Goff, S. L., Yang, J. C., Sherry, R. M., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.3024 · Cited by 569
Self-citationGasdermin E–mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome
Liu, Y., Fang, Y., Chen, X., Wang, Z., Liang, X., Zhang, T., Liu, M., Zhou, N., Lv, J., Tang, K., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aax7969 · Cited by 566
The pharmacology of second-generation chimeric antigen receptors
van der Stegen, S. J. C., Hamieh, M., & Sadelain, M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4597 · Cited by 577
Navigating CAR-T cells through the solid-tumour microenvironment
Hou, A. J., Chen, L. C., & Chen, Y. Y. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00189-2 · Cited by 580
Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies
Ruella, M., Barrett, D. M., Kenderian, S. S., Shestova, O. E., Hofmann, T. J., Perazzelli, J., Klichinsky, M., Aikawa, V., Nazimuddin, F., Kozlowski, M. S., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci87366 · Cited by 571
Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency
Feucht, J., Sun, J., Eyquem, J., Ho, Y.-J., Zhao, Z., Leibold, J., Dobrin, A., Cabriolu, A., Hamieh, M., & Sadelain, M. (2019) · Nature Medicine · doi:10.1038/s41591-018-0290-5 · Cited by 547
Hartmann, J., Schüßler‐Lenz, M., Bondanza, A., & Buchholz, C. J. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201607485 · Cited by 551
Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
Benmebarek, M.-R., Karches, C. H., Cadilha, B. L., Lesch, S., Endres, S., & Kobold, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061283 · Cited by 557
Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies
Zappasodi, R., Merghoub, T., & Wolchok, J. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.005 · Cited by 525
Chimeric antigen receptor T-cell therapies for lymphoma
Brudno, J. N., & Kochenderfer, J. N. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.128 · Cited by 522
Self-citationPhase I trials using Sleeping Beauty to generate CD19-specific CAR T cells
Kebriaei, P., Singh, H., Huls, M. H., Figliola, M. J., Bassett, R. L., Olivares, S., Jena, B., Dawson, M. J., Kumaresan, P. R., Su, S., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86721 · Cited by 508
Self-citationPotent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas
Mount, C., Majzner, R. G., Sundaresh, S., Arnold, E. P., Kadapakkam, M., Haile, S. T., Labanieh, L., Hulleman, E., Woo, P. J., Rietberg, S. P., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0006-x · Cited by 522
Self-citationRecent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy
Durgeau, A., Virk, Y., Corgnac, S., & Mami‐Chouaib, F. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00014 · Cited by 507
Salter, A. I., Ivey, R. G., Kennedy, J. J., Voillet, V., Rajan, A., Alderman, E. J., Voytovich, U. J., Lin, C., Sommermeyer, D., Liu, L., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aat6753 · Cited by 503
Side-effect management of chimeric antigen receptor (CAR) T-cell therapy
Schubert, M., Schmitt, M. W., Wang, L., Ramos, C. A., Jordan, K., Müller‐Tidow, C., & Dreger, P. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.10.478 · Cited by 502
Engineering CAR-T cells: Design concepts
Srivastava, S., & Riddell, S. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.06.004 · Cited by 506
Fitzgerald, J. C., Weiss, S. L., Maude, S. L., Barrett, D. M., Lacey, S. F., Melenhorst, J. J., Shaw, P. A., Berg, R. A., June, C. H., Porter, D. L., et al. (2016) · Critical Care Medicine · doi:10.1097/ccm.0000000000002053 · Cited by 468
Metadata
- Authors
- Lee, D. W., Kochenderfer, J. N., Stetler-Stevenson, M., Cui, Y. K., Delbrook, C., Feldman, S. A., Fry, T. J., Orentas, R., Sabatino, M., Shah, N. N., Steinberg, S. M., Stroncek, D., Tschernia, N., Yuan, C., Zhang, H., Zhang, L., Rosenberg, S. A., Wayne, A. S., & Mackall, C. L.
- Affiliations
- National Institutes of Health (US)
- National Cancer Institute (US)
- University of Nevada, Reno (US)
- University of Southern California (US)
- Corresponding author
- Mackall, Crystal L
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 385
- Issue
- 9967
- Pages
- 517-528
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC7065359
- OpenAlex
- W2129702476
- Cited by
- 2,898
- References
- 37
- Citations by year
- 2026: 86 · 2025: 154 · 2024: 175 · 2023: 217 · 2022: 275 · 2021: 311 · 2020: 350 · 2019: 317 · 2018: 315 · 2017: 314 · 2016: 232 · 2015: 134
- FWCI
- 103.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- St. Baldrick's Foundation
- Entertainment Industry Foundation
- National Institutes of Health
- National Cancer Institute (Z01BC011072, Z01BC010566, Z01BC011024)
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD19 chimeric antigen receptor, CAR T-cell therapy, acute lymphoblastic leukemia, non-Hodgkin lymphoma, relapsed or refractory B-cell malignancies, maximum tolerated dose, cytokine release syndrome, neurotoxicity, non-relapse mortality, fludarabine and cyclophosphamide conditioning
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Chimera, Feasibility Studies, Female, Humans, Infant, Lymphoma, Non-Hodgkin, Male, Receptors, Antigen, T-Cell, T-Lymphocytes, Cohort Studies, Treatment Outcome, Antigens, CD19, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Young Adult, Cell- and Tissue-Based Therapy
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