Engineering CAR-T cells
Open accessAbstract
Chimeric antigen receptor redirected T cells (CAR-T cells) have achieved inspiring outcomes in patients with B cell malignancies, and are now being investigated in other hematologic malignancies and solid tumors. CAR-T cells are generated by the T cells from patients' or donors' blood. After the T cells are expanded and genetically modified, they are reinfused into the patients. However, many challenges still need to be resolved in order for this technology to gain widespread adoption. In this review, we first discuss the structure and evolution of chimeric antigen receptors. We then report on the tools used for production of CAR-T cells. Finally, we address the challenges posed by CAR-T cells.
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?
Recently, multiple clinical trials used third-generation, self-inactivating LVVs to introduce genes into hematopoietic stem cells to correct primary immunodeficiencies and hemoglobinopathies.
“Recently, multiple clinical trials used third-generation, self-inactivating LVVs to introduce genes into hematopoietic stem cells to correct primary immunodeficiencies and hemoglobinopathies.”
From Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges (2020) · cites this paper as [104]
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–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
A 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
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
Morgan, 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 2,542 · see citing works
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 · see citing works
Porter, 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 · see citing works
Eshhar, Z., Waks, T., Gross, G., & Schindler, D. G. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.720 · Cited by 1,668 · 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
A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer
Kershaw, M. H., Westwood, J. A., Parker, L. L., Wang, G., Eshhar, Z., Mavroukakis, S. A., White, D. E., Wunderlich, J. R., Canevari, S., Rogers-Freezer, L. J., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1183 · Cited by 1,254 · see citing works
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 1,234 · see citing works
Pulè, M. A., Savoldo, B., Myers, G. D., Rössig, C., Russell, H. V., Dotti, G., Huls, M. H., Liu, E., Gee, A. P., Mei, Z., et al. (2008) · Nature Medicine · doi:10.1038/nm.1882 · Cited by 1,195 · see citing works
Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits
Roybal, K. T., Rupp, L. J., Morsut, L., Walker, W. J., McNally, K. A., Park, J. S., & Lim, W. A. (2016) · Cell · doi:10.1016/j.cell.2016.01.011 · Cited by 1,010 · see citing works
Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors
Morsut, L., Roybal, K. T., Xiong, X., Gordley, R. M., Coyle, S. M., Thomson, M., & Lim, W. A. (2016) · Cell · doi:10.1016/j.cell.2016.01.012 · Cited by 1,002 · see citing works
The role of TNF superfamily members in T-cell function and diseases
Croft, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2526 · Cited by 924 · 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
Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes
Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E. S., Ittmann, M., Marchetti, D., & Dotti, G. (2015) · Nature Medicine · doi:10.1038/nm.3833 · Cited by 820 · see citing works
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
Acuto, O., & Michel, F. (2003) · Nature Reviews Immunology · doi:10.1038/nri1248 · Cited by 775 · see citing works
Global Manufacturing of CAR T Cell Therapy
Levine, B. L., Miskin, J., Wonnacott, K., & Keir, C. (2017) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2016.12.006 · Cited by 765 · see citing works
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 750 · see citing works
Till, B. G., Jensen, M. C., Wang, J., Chen, E., Wood, B. L., Greisman, H. A., Qian, X., James, S. E., Raubitschek, A. A., Forman, S. J., et al. (2008) · Blood · doi:10.1182/blood-2007-12-128843 · Cited by 721 · see citing works
An overview of current delivery systems in cancer gene therapy
El‐Aneed, A. (2003) · Journal of Controlled Release · doi:10.1016/j.jconrel.2003.09.013 · Cited by 694 · see citing works
Park, J. R., DiGiusto, D. L., Slovak, M. L., Wright, C. L., Naranjo, A., Wagner, J. R., Meechoovet, H. B., Bautista, C., Chang, W.-C., Ostberg, J. R., et al. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300104 · Cited by 603 · 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
Till, B. G., Jensen, M. C., Wang, J., Qian, X., Gopal, A. K., Maloney, D. G., Lindgren, C. G., Lin, Y., Pagel, J. M., Budde, L. E., et al. (2012) · Blood · doi:10.1182/blood-2011-10-387969 · Cited by 531 · see citing works
Finney, H. M., Akbar, A. N., & Lawson, A. D. G. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.1.104 · Cited by 468 · see citing works
Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies
Rodgers, D. T., Mazagova, M., Hampton, E. N., Cao, Y. J., Ramadoss, N. S., Hardy, I. R., Schulman, A. D., Du, J., Wang, F., Singer, O., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524155113 · Cited by 398 · see citing works
New development in CAR-T cell therapy
Wang, Z., Wu, Z., Liu, Y., & Han, W. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0423-1 · Cited by 395 · 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
A robust system for production of minicircle DNA vectors
Kay, M. A., He, C.-Y., & Chen, Z.-Y. (2010) · Nature Biotechnology · doi:10.1038/nbt.1708 · Cited by 329 · see citing works
Frigault, M. J., Lee, J., Basil, M. C., Carpenito, C., Motohashi, S., Scholler, J., Kawalekar, O. U., Guedan, S., McGettigan, S. E., Posey, A. D., et al. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0186 · Cited by 324 · see citing works
(2013) · PubMed · Cited by 308 · see citing works
Chimeric antigen receptor T cells: a novel therapy for solid tumors
Yu, S., Li, A., Liu, Q., Li, T., Yuan, X., Han, X., & Wu, K. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0444-9 · Cited by 306 · see citing works
Zhao, Y., Wang, Q. J., Yang, S., Kochenderfer, J. N., Zheng, Z., Zhong, X., Sadelain, M., Eshhar, Z., Rosenberg, S. A., & Morgan, R. A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900447 · Cited by 292 · see citing works
Bridgeman, J. S., Hawkins, R. E., Bagley, S., Blaylock, M. G., Holland, M., & Gilham, D. E. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901766 · Cited by 267 · see citing works
Treating cancer with genetically engineered T cells
Park, T. S., Rosenberg, S. A., & Morgan, R. A. (2011) · Trends in biotechnology · doi:10.1016/j.tibtech.2011.04.009 · Cited by 218 · 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
Newick, K., O’Brien, S., Sun, J., Kapoor, V., Maceyko, S., Lo, A., Puré, E., Moon, E. K., & Albelda, S. Μ. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0263 · Cited by 197 · see citing works
Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy
Ramos, C. A., & Dotti, G. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.573476 · Cited by 183 · see citing works
Chen, Z.-Y., He, C.-Y., & Kay, M. A. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.126 · Cited by 180 · see citing works
Hu, Y., Sun, J., Wu, Z., Yu, J., Cui, Q., Pu, C., Liang, B., Luo, Y., Shi, J., Jin, A., et al. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0299-5 · Cited by 178 · see citing works
Brocker, T. (2000) · Blood · doi:10.1182/blood.v96.5.1999 · Cited by 173 · see citing works
Marin, V., Pizzitola, I., Agostoni, V., et al. (2010) · Haematologica · doi:10.3324/haematol.2010.026310 · Cited by 132 · see citing works
Levine, B. L. (2015) · Cancer Gene Therapy · doi:10.1038/cgt.2015.5 · Cited by 126 · see citing works
Design of Retroviral Vectors and Helper Cells for Gene Therapy
Hu, W.-S., & Pathak, V. K. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01467-4 · Cited by 124 · see citing works
Tasian, S. K., & Gardner, R. A. (2015) · Therapeutic Advances in Hematology · doi:10.1177/2040620715588916 · Cited by 117 · see citing works
Li, J., Zhong, J. F., Zhang, X., & Zhang, C. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0405-3 · Cited by 112 · see citing works
Self-citationDNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer
Wang, G. P., Garrigue, A., Ciuffi, A., Ronen, K., Leipzig, J., Berry, C., Lagresle-Peyrou, C., Benjelloun, F., Hacein-Bey-Abina, S., Fischer, A., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn125 · Cited by 110 · 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
Fifteen Years of Gene Therapy Based on Chimeric Antigen Receptors: “Are We Nearly There Yet?”
Dotti, G., Savoldo, B., & Brenner, M. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.142 · Cited by 105 · see citing works
Targeted immunotherapy of cancer with CAR T cells: achievements and challenges
Lipowska-Bhalla, G., Gilham, D., Hawkins, R., & Rothwell, D. (2012) · Cancer Immunology and Immunotherapy · doi:10.1007/s00262-012-1254-0 · Cited by 105 · see citing works
Vectors and strategies for nonviral cancer gene therapy
Pahle, J., & Walther, W. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2016.1134480 · Cited by 104 · 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
Lamers, C. H. J., Langeveld, S. C. L., Ruijven, C. M. G.-V., Debets, R., Sleijfer, S., & Gratama, J. W. (2007) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-007-0330-3 · Cited by 94 · see citing works
Cai, B., Guo, M., Wang, Y., Zhang, Y., Yang, J. J. J., Guo, Y., Dai, H., Yu, C., Sun, Q., Qiao, J., et al. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0357-z · Cited by 64 · see citing works
Heuser-Loy, C., Hombach, A. A., Lösch, C., et al. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302023 · Cited by 53 · 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
Kato, D., Yaguchi, T., Iwata, T., Morii, K., Nakagawa, T., Nishimura, R., & Kawakami, Y. (2017) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.40.68 · Cited by 27 · see citing works
Chimaeric antigen receptor T-cell therapy for tumour immunotherapy
Sha, H., Wang, D., Yan, D., Hu, Y., Yang, S., Liu, S.-W., & Feng, J. (2017) · Bioscience Reports · doi:10.1042/bsr20160332 · Cited by 20 · 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
Frigault, M. J., Lee, J., Basil, M. C., Carpenito, C., Scholler, J., Kawalekar, O. U., Guedan, S., McGettigan, S. E., Ang, S., Cooper, L. J. N., et al. (2015) · Cited by 7 · see citing works
Automated Lentiviral Transduction of T Cells with Cars Using the Clinimacs Prodigy
Mock, U., Nickolay, L., Cheung, G.-K., et al. (2015) · UCL Discovery (University College London) · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
CAR T cells in solid tumors: challenges and opportunities
Marofi, F., Motavalli, R., Safonov, V. A., Thangavelu, L., Yumashev, A. V., Alexander, M., Shomali, N., Chartrand, M. S., Pathak, Y., Jarahian, M., et al. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02128-1 · Cited by 582 · see citing works
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510 · see citing works
CAR T‐Cell‐Based gene therapy for cancers: new perspectives, challenges, and clinical developments
Jogalekar, M. P., Rajendran, R. L., Khan, F., Dmello, C., Gangadaran, P., & Ahn, B.-C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.925985 · Cited by 214 · 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
CAR T-cell therapy in hematologic malignancies: a voyage in progress.
Holstein, S. A., & Lunning, M. A. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1674 · Cited by 172 · see citing works
Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy
Yilmaz, A., Cui, H., Caligiuri, M. A., & Yu, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00998-9 · Cited by 171 · see citing works
Novel immunomodulatory drugs and neo-substrates
Gao, S., Wang, S., & Song, Y. (2020) · Biomarker Research · doi:10.1186/s40364-020-0182-y · Cited by 95 · see citing works
High-efficiency nonviral CRISPR/Cas9-mediated gene editing of human T cells using plasmid donor DNA
Oh, S. A., Senger, K., Madireddi, S., Akhmetzyanova, I., Ishizuka, I. E., Tarighat, S., Lo, J. H., Shaw, D., Haley, B., & Rutz, S. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20211530 · Cited by 88 · see citing works
Elsallab, M., Levine, B. L., Wayne, A. S., & Abou-El-Enein, M. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30729-6 · Cited by 81 · see citing works
Immune checkpoint inhibitors for multiple myeloma immunotherapy
Liu, Z., Xu, X., Liu, H., Zhao, X., Yang, C., & Fu, R. (2023) · Experimental Hematology & Oncology · doi:10.1186/s40164-023-00456-5 · Cited by 40 · see citing works
CAR-Treg cell therapies and their future potential in treating ocular autoimmune conditions
Abraham, A. R., Maghsoudlou, P., Copland, D. A., Nicholson, L. B., & Dick, A. D. (2023) · Frontiers in Ophthalmology · doi:10.3389/fopht.2023.1184937 · Cited by 20 · see citing works
CRISPR-Cas9 genome editing for cancer immunotherapy: opportunities and challenges
Chen, M., Xu, J., Zhou, Y., Zhang, S., & Zhu, D. (2020) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz027 · Cited by 12 · see citing works
- Authors
- Zhang, C., Liu, J., Zhong, J. F., & Zhang, X.
- Affiliations
- Army Medical University (CN)
- University of Southern California (US)
- Corresponding author
- Zhang, Xi
- Venue
- Biomarker Research
- Published
- 2017-06-24
- Volume
- 5
- Issue
- 1
- Pages
- 22-22
- ISSN
- 2050-7771 (ISSN-L)
- PMC
- PMC5482931
- OpenAlex
- W2688905162
- Cited by
- 578
- References
- 61
- Citations by year
- 2026: 40 · 2025: 71 · 2024: 104 · 2023: 71 · 2022: 91 · 2021: 50 · 2020: 61 · 2019: 53 · 2018: 31 · 2017: 6
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Biomarker Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- the clinical key foundation of Xinqiao Hospital of Third Military Medical University (2016YLC03)
- 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 › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- chimeric antigen receptor T cells, chimeric antigen receptor, T cell engineering, hematologic malignancies, solid tumors, B-cell malignancies, T cell expansion, genetic modification
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
