Global Manufacturing of CAR T Cell Therapy
Open accessAbstract
Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion. Additionally, the challenges of taking a chimeric antigen receptor T cell manufacturing process from a single institution to a large-scale multi-site manufacturing center must be addressed. We have anticipated such concerns in our experience with the CD19 chimeric antigen receptor T cell therapy CTL019. In this review, we discuss steps involved in the cell processing of the technology, including the use of an optimal vector for consistent cell processing, along with addressing the challenges of expanding chimeric antigen receptor T cell therapy to a global patient population.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Autologous CAR T cells have sometimes suffered manufacturing delays and, in some instances, had difficulty meeting target doses in commercial production.
“Despite clinical success, autologous CAR T cells have sometimes suffered manufacturing delays and, in some instances, had difficulty meeting target doses in commercial production (23).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [23]
The sections on scaling manufacturing and ensuring product quality discuss potential challenges, but do not report manufacturing delays or instances in which commercial production failed to meet target CAR T-cell doses. Searches for delays, dose, and target specifications found no passage establishing those events; the target-specifications passage concerns viral vector production instead. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe LVVs have been used to alter T cells by introducing genes to generate immunity to fight cancer through the delivery of chimeric antigen receptors (CARs) or cloned T-cell receptors.
“The LVVs have been used to alter T cells by introducing genes to generate immunity to fight cancer through the delivery of chimeric antigen receptors (CARs) or cloned T-cell receptors.”
From Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges (2020) · cites this paper as [105]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413 · see citing works
Self-citationChimeric 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 · see citing works
Self-citationA Third-Generation Lentivirus Vector with a Conditional Packaging System
Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., & Naldini, L. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8463-8471.1998 · Cited by 3,341 · see citing works
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., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61403-3 · Cited by 2,898 · see citing works
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 · see citing works
Efficacy 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 2,484 · see citing works
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 2,389 · see citing works
Self-citationLong, 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 · see citing works
Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery
Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L., & Trono, D. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9873-9880.1998 · Cited by 1,815 · see citing works
Gross, G., Waks, T., & Eshhar, Z. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.10024 · Cited by 1,597 · see citing works
Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy
Di Stasi, A., Tey, S.-K., Dotti, G., Fujita, Y., Kennedy-Nasser, A., Martinez, C., Straathof, K., Liu, E., Durett, A. G., Grilley, B., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106152 · Cited by 1,512 · see citing works
The basic principles of chimeric antigen receptor (CAR) design
Sadelain, M., Brentjens, R., & Rivière, I. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0548 · Cited by 1,423 · see citing works
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 1,038 · see citing works
Beatty, G. L., Haas, A. R., Maus, M. V., Torigian, D. A., Soulen, M. C., Plesa, G., Chew, A., Zhao, Y., Levine, B. L., Albelda, S. Μ., et al. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0170 · Cited by 867 · see citing works
Self-citationKloss, C. C., Condomines, M., Cartellieri, M., Bachmann, M. P., & Sadelain, M. (2012) · Nature Biotechnology · doi:10.1038/nbt.2459 · Cited by 860 · see citing works
Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T Cells
Scholler, J., Brady, T., Binder-Scholl, G. K., Hwang, W., Plesa, G., Hege, K. M., Vogel, A. N., Kalos, M. D., Riley, J. L., Deeks, S. G., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003761 · Cited by 651 · see citing works
Self-citationPoirot, 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 · see citing works
Montini, E., Cesana, D., Schmidt, M., Sanvito, F., Bartholomae, C. C., Ranzani, M., Benedicenti, F., Sergi, L. S., Ambrosi, A., Ponzoni, M., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37630 · Cited by 571 · see citing works
Hoyos, V., Savoldo, B., Quintarelli, C., Mahendravada, A., Zhang, M., Vera, J. F., Heslop, H., Rooney, C. M., Brenner, M. K., & Dotti, G. (2010) · Leukemia · doi:10.1038/leu.2010.75 · Cited by 568 · see citing works
Finney, H. M., Lawson, A. D. G., Bebbington, C. R., & Weir, A. N. C. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.6.2791 · Cited by 549 · see citing works
Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells.
Yu, S. F., von Rüden, T., Kantoff, P. W., Garber, C., Seiberg, M., Rüther, U., Anderson, W. F., Wagner, E. F., & Gilboa, E. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.10.3194 · Cited by 541 · see citing works
Maus, M. V., Thomas, A., Leonard, D. G. B., Allman, D., Addya, K., Schlienger, K., Riley, J. L., & June, C. H. (2002) · Nature Biotechnology · doi:10.1038/nbt0202-143 · Cited by 455 · see citing works
Kuwana, Y., Asakura, Y., Utsunomiya, N., Nakanishi, M., Arata, Y., Itoh, S., Nagase, F., & Kurosawa, Y. (1987) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(87)90502-x · Cited by 432 · see citing works
ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells
Guedan, S., Chen, X., Madar, A., Carpenito, C., McGettigan, S. E., Frigault, M. J., Lee, J., Posey, A. D., Scholler, J., Scholler, N., et al. (2014) · Blood · doi:10.1182/blood-2013-10-535245 · Cited by 348 · see citing works
Levine, B. L., Bernstein, W. B., Connors, M., Craighead, N., Lindsten, T., Thompson, C. B., & June, C. H. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.12.5921 · Cited by 340 · see citing works
Self-citation(2013) · PubMed · Cited by 308 · see citing works
Minimal Requirement for a Lentivirus Vector Based on Human Immunodeficiency Virus Type 1
Kim, V. N., Mitrophanous, K. A., Kingsman, S. M., & Kingsman, A. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.1.811-816.1998 · Cited by 269 · see citing works
Suhoski, M. M., Golovina, T. N., Aqui, N. A., Tai, V. C., Varela-Rohena, A., Milone, M. C., Carroll, R. G., Riley, J. L., & June, C. H. (2007) · Molecular Therapy · doi:10.1038/mt.sj.6300134 · Cited by 266 · see citing works
VARMUS, H. E., Quintrell, N. A., & Ortiz, S. (1981) · Cell · doi:10.1016/0092-8674(81)90228-2 · Cited by 241 · see citing works
Kotsopoulou, E., Kim, V. N., Kingsman, A. J., Kingsman, S. M., & Mitrophanous, K. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.10.4839-4852.2000 · Cited by 228 · see citing works
Anticoagulation techniques in apheresis: From heparin to citrate and beyond
Lee, G., & Arepally, G. M. (2012) · Journal of Clinical Apheresis · doi:10.1002/jca.21222 · Cited by 207 · see citing works
Towards a commercial process for the manufacture of genetically modified T cells for therapy
Kaiser, A., Assenmacher, M., Schröder, B., Meyer, M., Orentas, R. J., Bethke, U., & Dropulić, B. (2015) · Cancer Gene Therapy · doi:10.1038/cgt.2014.78 · Cited by 202 · see citing works
Budde, L. E., Berger, C., Lin, Y., Wang, J., Lin, X., Frayo, S. E., Brouns, S. A., Spencer, D. M., Till, B. G., Jensen, M. C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082742 · Cited by 187 · see citing works
Biosafety Features of Lentiviral Vectors
Schambach, A., Zychlinski, D., Ehrnstroem, B., & Baum, C. (2013) · Human Gene Therapy · doi:10.1089/hum.2012.229 · Cited by 173 · see citing works
Singh, H., Figliola, M. J., Dawson, M. J., Olivares, S., Zhang, L., Yang, G., Maiti, S. N., Manuri, P. R., Senyukov, V., Jena, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064138 · Cited by 170 · see citing works
Jin, J., Sabatino, M., Somerville, R. P. T., Wilson, J. R., Dudley, M. E., Stroncek, D. F., & Rosenberg, S. A. (2012) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31824e801f · Cited by 151 · see citing works
Activation of the c- myb Locus by Viral Insertional Mutagenesis in Plasmacytoid Lymphosarcomas
Shen-Ong, G. L. C., Potter, M., Mushinski, J. F., Lavu, S., & Reddy, E. P. (1984) · Science · doi:10.1126/science.6093260 · Cited by 143 · see citing works
The Sleeping Beauty transposon system: a non-viral vector for gene therapy
Aronovich, E. L., McIvor, R. S., & Hackett, P. B. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr140 · Cited by 143 · see citing works
Levine, B. L. (2015) · Cancer Gene Therapy · doi:10.1038/cgt.2015.5 · Cited by 126 · see citing works
Self-citationAdoptive Therapy With Chimeric Antigen Receptor–Modified T Cells of Defined Subset Composition
Riddell, S. R., Sommermeyer, D., Berger, C., Liu, L., Balakrishnan, A., Salter, A. I., Hudecek, M., Maloney, D. G., & Turtle, C. J. (2014) · The Cancer Journal · doi:10.1097/ppo.0000000000000036 · Cited by 113 · see citing works
Patient monitoring and follow‐up in lentiviral clinical trials
McGarrity, G. J., Hoyah, G., Winemiller, A., Andre, K., Stein, D., Blick, G., Greenberg, R. N., Kinder, C., Zolopa, A., Binder‐Scholl, G., et al. (2013) · The Journal of Gene Medicine · doi:10.1002/jgm.2691 · Cited by 109 · see citing works
First Clinical Application of Talen Engineered Universal CAR19 T Cells in B-ALL
Qasim, W., Amrolia, P. J., Samarasinghe, S., et al. (2015) · Blood · doi:10.1182/blood.v126.23.2046.2046 · Cited by 98 · see citing works
Optimizing the production of suspension cells using the G-Rex “M” series
Bajgain, P., Mucharla, R., Wilson, J., Welch, D., Anurathapan, U., Liang, B., Lu, X., Ripple, K., Centanni, J. M., Hall, C., et al. (2014) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2014.15 · Cited by 95 · see citing works
Somerville, R. P. T., Devillier, L., Parkhurst, M. R., Rosenberg, S. A., & Dudley, M. E. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-69 · Cited by 94 · see citing works
Grupp, S. A., Laetsch, T. W., Buechner, J., et al. (2016) · Blood · doi:10.1182/blood.v128.22.221.221 · Cited by 83 · see citing works
Maude, S. L., Pulsipher, M. A., Boyer, M. W., Grupp, S. A., Davies, S. M., Phillips, C. L., Verneris, M. R., August, K. J., Schlis, K. D., Driscoll, T. A., et al. (2016) · Blood · doi:10.1182/blood.v128.22.2801.2801 · Cited by 75 · see citing works
Self-citationLarge-scale Clinical-grade Retroviral Vector Production in a Fixed-Bed Bioreactor
Wang, X., Olszewska, M., Qu, J., Wasielewska, T., Bartido, S., Hermetet, G., Sadelain, M., & Rivière, I. (2015) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000072 · Cited by 70 · see citing works
GMP production and testing of Xcellerated T Cells™ for the treatment of patients with CLL
Hami, L., Green, C., Leshinsky, N., Markham, E., Miller, K., & Craig, S. (2004) · Cytotherapy · doi:10.1080/14653240410005348 · Cited by 66 · see citing works
Bear, A. S., Morgan, R. A., Cornetta, K., June, C. H., Binder-Scholl, G., Dudley, M. E., Feldman, S. A., Rosenberg, S. A., Shurtleff, S. A., Rooney, C. M., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2011.288 · Cited by 59 · see citing works
Huls, M. H., Figliola, M. J., Dawson, M. J., Olivares, S., Kebriaei, P., Shpall, E. J., Champlin, R. E., Singh, H., & Cooper, L. J. N. (2013) · Journal of Visualized Experiments · doi:10.3791/50070 · Cited by 53 · see citing works
Powell, D. J., Brennan, A. L., Zheng, Z., Huynh, H. A., Cotte, J., & Levine, B. L. (2009) · Cytotherapy · doi:10.3109/14653240903188921 · Cited by 51 · see citing works
Self-citationSomerville, R. P. T., & Dudley, M. E. (2012) · OncoImmunology · doi:10.4161/onci.21206 · Cited by 34 · see citing works
Przybylowski, M., Hakakha, A., Stefanski, J., Hodges, J., Sadelain, M., & Rivière, I. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302648 · Cited by 34 · see citing works
Apheresis Techniques and Cellular Immunomodulation
Smith, J. W. (1997) · Therapeutic Apheresis and Dialysis · doi:10.1111/j.1744-9987.1997.tb00137.x · Cited by 24 · see citing works
Retroviral vectors for clinical immunogene therapy are stable for up to 9 years
Lamers, C. H. J., van Elzakker, P., Luider, B. A., van Steenbergen, S. C. L., Sleijfer, S., Debets, R., & Gratama, J. W. (2008) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7701114 · Cited by 16 · see citing works
Turtle, C. J., Berger, C., Sommermeyer, D., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.3006 · Cited by 15 · see citing works
Gouble, A., Philip, B., Poirot, L., et al. (2014) · Blood · doi:10.1182/blood.v124.21.4689.4689 · Cited by 9 · see citing works
(2007) · Wiley eBooks · doi:10.1002/9780470184585 · Cited by 8 · see citing works
Automated Lentiviral Transduction of T Cells with Cars Using the Clinimacs Prodigy
Mock, U., Nickolay, L. E., Cheung, G. W.-K., et al. (2015) · Blood · doi:10.1182/blood.v126.23.2043.2043 · Cited by 8 · see citing works
Personalized Cell-Based Medicine: Activated and Expanded T Cells for Adoptive Immunotherapy
Levine, B. L. (2007) · BioProcessing Journal · doi:10.12665/j62.levine · Cited by 6 · see citing works
Self-citationAssays for the Release of Cellular Gene Therapy Products
Cross, P. J., & Levine, B. L. (2007) · doi:10.1002/9780470184585.ch26 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [23]Coffin J. Hughes S. Varmus H. Retroviruses 1997 Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY 21433340
Cited by
Sorted by citations
The evolution of commercial drug delivery technologies
Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361 · see citing works
Clinical use of lentiviral vectors
Milone, M. C., & O’Doherty, U. (2018) · Leukemia · doi:10.1038/s41375-018-0106-0 · Cited by 930 · see citing works
“Following purification, the eluted fractions undergo a series of filtration steps for sterilization purposes and to remove any remaining cellular debris [62, 63].”
BackgroundZhang, C., Liu, J., Zhong, J. F., & Zhang, X. (2017) · Biomarker Research · doi:10.1186/s40364-017-0102-y · Cited by 578 · see citing works
Shah, N., Chari, A., Scott, E., Mezzi, K., & Usmani, S. Z. (2020) · Leukemia · doi:10.1038/s41375-020-0734-z · Cited by 490 · 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
Ghosh, S., Brown, A. M., Jenkins, C., & Campbell, K. (2020) · Applied Biosafety · doi:10.1177/1535676019899502 · Cited by 218 · see citing works
Derraz, B., Breda, G., Kaempf, C., Baenke, F., Cotte, F., Reiche, K., Köhl, U., Kather, J. N., Eskenazy, D., & Gilbert, S. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00517-w · Cited by 94 · see citing works
Approval of First CAR-Ts: Have we Solved all Hurdles for ATMPs?
Seimetz, D., Heller, K., & Richter, J. (2019) · Cell Medicine · doi:10.1177/2155179018822781 · Cited by 90 · see citing works
Promises and challenges of a decentralized CAR T-cell manufacturing model
Shah, M., Krull, A., Odonnell, L., de Lima, M. J., & Bezerra, E. (2023) · Frontiers in Transplantation · doi:10.3389/frtra.2023.1238535 · Cited by 77 · see citing works
Tipanee, J., Samara-Kuko, E., Gevaert, T., Chuah, M. K., & VandenDriessche, T. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.06.006 · Cited by 76 · see citing works
Si, K., Dai, Z., Li, Z., Ye, Z., Ding, B., Feng, S., Sun, B., Shen, Y., & Xiao, Z. (2023) · Cytotherapy · doi:10.1016/j.jcyt.2023.01.005 · Cited by 60 · see citing works
Wang, K., Liu, Y., Li, J., Wang, B., Bishop, R., White, C., Das, A., Levine, A. D., Ho, L., Levine, B. L., et al. (2019) · Cytotherapy · doi:10.1016/j.jcyt.2019.07.002 · Cited by 29 · see citing works
Self-citationBaras, A., Bocket, L., Beauvais, D., Hallaert, C., Varlet, P., Yakoub-Agha, I., Hober, D., & Alidjinou, E. K. (2021) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2020.12.004 · Cited by 14 · see citing works
Manufacturing of CAR-T cells using in-house vectors and the CliniMACS Prodigy
Kerbauy, L. N., & Mesquita, F. P. (2026) · JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY · doi:10.46765/2675-374x.2025v7n1e338
Sotomayor, P., Prochazka, L., & Brockhaus, M. (2022) · Pharma Research · doi:10.62655/s-epub.2022.v14.i01.pp53-62
- Authors
- Levine, B. L., Miskin, J., Wonnacott, K., & Keir, C.
- Affiliations
- University of Pennsylvania (US)
- Oxford BioMedica (United Kingdom) (GB)
- Corresponding author
- Levine, Bruce L.
- ORCID
- Levine, Bruce L.
- Venue
- Molecular Therapy - Methods & Clinical Development
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 4
- Pages
- 92-101
- ISSN
- 2329-0501 (ISSN-L)
- PMC
- PMC5363291
- OpenAlex
- W2567664749
- Cited by
- 765
- References
- 61
- Citations by year
- 2026: 80 · 2025: 85 · 2024: 100 · 2023: 98 · 2022: 79 · 2021: 88 · 2020: 83 · 2019: 68 · 2018: 65 · 2017: 15 · 2013: 1
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Therapy — Methods & Clinical Development (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Novartis Pharmaceuticals
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- CAR T-cell therapy, chimeric antigen receptor, cell manufacturing, regulatory compliance, CD19, tisagenlecleucel, multi-objective optimization, B-cell malignancies, hematologic malignancies, solid tumors, cell processing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review