Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering
Open accessAbstract
Chimeric antigen receptor (CAR) T cell therapy relies on the ex vivo manipulation of patient T cells to create potent, cancer-targeting therapies, shown to be capable of inducing remission in patients with acute lymphoblastic leukemia and large B cell lymphoma. However, current CAR T cell engineering methods use viral delivery vectors, which induce permanent CAR expression and could lead to severe adverse effects. Messenger RNA (mRNA) has been explored as a promising strategy for inducing transient CAR expression in T cells to mitigate the adverse effects associated with viral vectors, but it most commonly requires electroporation for T cell mRNA delivery, which can be cytotoxic. Here, ionizable lipid nanoparticles (LNPs) were designed for ex vivo mRNA delivery to human T cells. A library of 24 ionizable lipids was synthesized, formulated into LNPs, and screened for luciferase mRNA delivery to Jurkat cells, revealing seven formulations capable of enhanced mRNA delivery over lipofectamine. The top-performing LNP formulation, C14–4, was selected for CAR mRNA delivery to primary human T cells. This platform induced CAR expression at levels equivalent to electroporation, with substantially reduced cytotoxicity. CAR T cells engineered via C14–4 LNP treatment were then compared to electroporated CAR T cells in a coculture assay with Nalm-6 acute lymphoblastic leukemia cells, and both CAR T cell engineering methods elicited potent cancer-killing activity. These results demonstrate the ability of LNPs to deliver mRNA to primary human T cells to induce functional protein expression, and indicate the potential of LNPs to enhance mRNA-based CAR T cell engineering methods.
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Lipid nanoparticle-mRNA formulations have been investigated for ex vivo engineering of CAR T cells and for the production of antibodies, such as anti-CD20, anti-human epidermal growth factor receptor 2 and anti-CD3/claudin 6.
“Lipid nanoparticle–mRNA formulations have also been investigated for ex vivo engineering of CAR T cells217 and for the production of antibodies, such as anti-CD20 (ref.146), anti-human epidermal growth factor receptor 2 (HER2)95 and anti-CD3/claudin 6 (ref.147).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [217]
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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-citationmRNA vaccines — a new era in vaccinology
Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.243 · Cited by 4,667 · see citing works
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
Self-citationLee, 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
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728 · see citing works
Delivery technologies for cancer immunotherapy
Riley, R., June, C. H., Langer, R., & Mitchell, M. J. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0006-z · Cited by 2,621 · see citing works
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 2,542 · see citing works
mRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474 · see citing works
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy
Brown, C. E., Alizadeh, D., Starr, R., Weng, L., Wagner, J. R., Naranjo, A., Ostberg, J. R., Blanchard, M. S., Kilpatrick, J., Simpson, J., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1610497 · Cited by 1,842 · see citing works
Gilleron, J., Querbes, W., Zeigerer, A., Borodovsky, A., Marsico, G., Schubert, U., Manygoats, K., Seifert, S., Andree, C., Stöter, M., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2612 · Cited by 1,681 · see citing works
Endosomal escape pathways for delivery of biologicals
Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.004 · Cited by 1,561 · see citing works
Milone, M. C., Fish, J. D., Carpenito, C., Carroll, R. G., Binder, G. K., Teachey, D., Samanta, M., Lakhal, M., Gloss, B., Danet-Desnoyers, G., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.83 · Cited by 1,197 · see citing works
Self-citationEngineered T cells: the promise and challenges of cancer immunotherapy
Fesnak, A. D., June, C. H., & Levine, B. L. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.97 · Cited by 1,074 · see citing works
Self-citationPardi, N., Tuyishime, S., Muramatsu, H., Kariko, K., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., & Weissman, D. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.007 · Cited by 1,014 · see citing works
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · 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-citationTherapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839 · see citing works
Tools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
Kauffman, K. J., Dorkin, J. R., Yang, J. H., Heartlein, M. W., DeRosa, F., Mir, F. F., Fenton, O. S., & Anderson, D. G. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b02497 · Cited by 785 · see citing works
Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy
Oberli, M. A., Reichmuth, A. M., Dorkin, J. R., Mitchell, M. J., Fenton, O. S., Jaklenec, A., Anderson, D. G., Langer, R., & Blankschtein, D. (2017) · Nano Letters · doi:10.1021/acs.nanolett.6b03329 · Cited by 719 · see citing works
Self-citationRuella, M., Xu, J., Barrett, D. M., Fraietta, J. A., Reich, T. J., Ambrose, D. E., Klichinsky, M., Shestova, O., Patel, P. R., Kulikovskaya, I., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0201-9 · Cited by 659 · see citing works
Self-citationChemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs
Shen, X., & Corey, D. R. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1239 · Cited by 639 · see citing works
Clinical manufacturing of CAR T cells: foundation of a promising therapy
Wang, X., & Rivière, I. (2016) · Molecular Therapy - Oncolytics · doi:10.1038/mto.2016.15 · Cited by 637 · see citing works
Jurkat T cells and development of the T-cell receptor signalling paradigm
Abraham, R. T., & Weiss, A. (2004) · Nature reviews. Immunology · doi:10.1038/nri1330 · Cited by 602 · see citing works
Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
Heyes, J., Palmer, L., Bremner, K., & MacLachlan, I. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.06.014 · Cited by 572 · see citing works
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 535 · see citing works
Design and development of therapies using chimeric antigen receptor‐expressing T cells
Dotti, G., Gottschalk, S. M., Savoldo, B., & Brenner, M. K. (2013) · Immunological Reviews · doi:10.1111/imr.12131 · Cited by 510 · see citing works
Mui, B. L., Tam, Y. K., Jayaraman, M., Ansell, S. M., Du, X., Tam, Y. Y. C., Lin, P. J. C., Chen, S., Narayanannair, J. K., Rajeev, K. G., et al. (2013) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2013.66 · Cited by 509 · see citing works
Anderson, D. G., Lynn, D. M., & Langer, R. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200351244 · Cited by 508 · see citing works
Zhao, Y., Moon, E. K., Carpenito, C., Paulos, C. M., Liu, X., Brennan, A. L., Chew, A., Carroll, R. G., Scholler, J., Levine, B. L., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2880 · Cited by 448 · see citing works
Self-citationChen, D. L., Love, K. T., Chen, Y., Eltoukhy, A. A., Kastrup, C. J., Sahay, G., Jeon, A., Dong, Y., Whitehead, K. A., & Anderson, D. G. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301621z · Cited by 422 · see citing works
Adoptive cellular therapy: A race to the finish line
June, C. H., Riddell, S. R., & Schumacher, T. N. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa3643 · Cited by 402 · see citing works
Self-citationMaterials for non-viral intracellular delivery of messenger RNA therapeutics
Kauffman, K. J., Webber, M. J., & Anderson, D. G. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.12.032 · Cited by 400 · see citing works
A guide to manufacturing CAR T cell therapies
Vormittag, P., Gunn, R., Ghorashian, S., & Veraitch, F. S. (2018) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2018.01.025 · Cited by 389 · see citing works
Brentjens, R. J., Yeh, R., Bernal, Y. J., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.31 · Cited by 380 · see citing works
The dynamic RNA modification 5‐methylcytosine and its emerging role as an epitranscriptomic mark
Trixl, L., & Lusser, A. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1510 · Cited by 364 · see citing works
Chimeric Antigen Receptor Therapy for Cancer
Barrett, D. M., Singh, N., Porter, D. L., Grupp, S. A., & June, C. H. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-060512-150254 · Cited by 350 · see citing works
Self-citationAvanzi, M. P., Yeku, O., Li, X., Wijewarnasuriya, D., van Leeuwen, D. G., Cheung, K., Park, H., Purdon, T. J., Daniyan, A. F., Spitzer, M. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.051 · Cited by 345 · see citing works
Biological gene delivery vehicles: beyond viral vectors.
Seow, Y., & Wood, M. (2009) · Molecular Therapy · doi:10.1038/mt.2009.41 · Cited by 339 · see citing works
Hollyman, D., Stefanski, J., Przybylowski, M., Bartido, S. M., Bórquez-Ojeda, O., Taylor, C., Yeh, R., Capacio, V., Olszewska, M., Hosey, J., et al. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e318194a6e8 · Cited by 316 · see citing works
Lipid Nanoparticle Formulations for Enhanced Co-delivery of siRNA and mRNA
Ball, R. L., Hajj, K. A., Vizelman, J., Bajaj, P., & Whitehead, K. A. (2018) · Nano Letters · doi:10.1021/acs.nanolett.8b01101 · Cited by 314 · see citing works
Hajj, K. A., Ball, R. L., Deluty, S. B., Singh, S. R., Strelkova, D., Knapp, C. M., & Whitehead, K. A. (2019) · Small · doi:10.1002/smll.201805097 · Cited by 312 · see citing works
Svitkin, Y. V., Cheng, Y. M., Chakraborty, T., Presnyak, V., John, M., & Sonenberg, N. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx135 · Cited by 278 · see citing works
Mechanogenetics for the remote and noninvasive control of cancer immunotherapy
Pan, Y., Yoon, S., Sun, J., Huang, Z., Lee, C., Allen, M., Wu, Y., Chang, Y., Sadelain, M., Shung, K. K., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714900115 · Cited by 268 · see citing works
Boosting intracellular delivery of lipid nanoparticle-encapsulated mRNA
Patel, S., Ashwanikumar, N., Robinson, E., DuRoss, A., Sun, C., Murphy-Benenato, K. E., Mihai, C., Almarsson, Ö., & Sahay, G. (2017) · Nano Letters · doi:10.1021/acs.nanolett.7b02664 · Cited by 251 · see citing works
McKinlay, C. J., Benner, N. L., Haabeth, O. A. W., Waymouth, R. M., & Wender, P. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1805358115 · Cited by 240 · see citing works
Cardarelli, F., Digiacomo, L., Marchini, C., et al. (2016) · Scientific Reports · doi:10.1038/srep25879 · Cited by 234 · see citing works
Clinical potential of electroporation for gene therapy and DNA vaccine delivery
Lambricht, L., Lopes, A., Kos, Š., et al. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1121990 · Cited by 231 · see citing works
FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma
Bouchkouj, N., Kasamon, Y. L., de Claro, R. A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2743 · Cited by 226 · see citing works
Cheng, Q., Wei, T., Jia, Y., Farbiak, L., Zhou, K., Zhang, S., Wei, Y., Zhu, H., & Siegwart, D. J. (2018) · Advanced Materials · doi:10.1002/adma.201805308 · Cited by 221 · see citing works
Treatment of Advanced Leukemia in Mice with mRNA Engineered T Cells
Barrett, D. M., Zhao, Y., Liu, X., Jiang, S., Carpenito, C., Kalos, M. D., Carroll, R. G., June, C. H., & Grupp, S. A. (2011) · Human Gene Therapy · doi:10.1089/hum.2011.070 · Cited by 220 · see citing works
Self-citationWang, T., Larcher, L. M., Ma, L., et al. (2018) · Molecules · doi:10.3390/molecules23102564 · Cited by 219 · see citing works
Lipid-based mRNA vaccine delivery systems
Midoux, P., & Pichon, C. (2014) · Expert Review of Vaccines · doi:10.1586/14760584.2015.986104 · Cited by 209 · see citing works
Biomaterials for vaccine-based cancer immunotherapy
Zhang, R., Billingsley, M. M., & Mitchell, M. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.10.008 · Cited by 201 · see citing works
Self-citationCationic polymers for non-viral gene delivery to human T cells
Olden, B. R., Cheng, Y., Yu, J. L., & Pun, S. H. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.02.043 · Cited by 197 · see citing works
Transient Gene Expression by Nonintegrating Lentiviral Vectors
Nightingale, S. J., Hollis, R. P., Pepper, K. A., Petersen, D., Yu, X.-J., Yang, C., Bahner, I., & Kohn, D. B. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.01.008 · Cited by 192 · see citing works
Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo
DiTommaso, T., Cole, J. M., Cassereau, L., Buggé, J. A., Hanson, J. L. S., Bridgen, D. T., Stokes, B., Loughhead, S. M., Beutel, B. A., Gilbert, J. B., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1809671115 · Cited by 186 · see citing works
Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers
Moffett, H. F., Coon, M. E., Radtke, S., Stephan, S. B., McKnight, L. E., Lambert, A. R., Stoddard, B. L., Kiem, H., & Stephan, M. T. (2017) · Nature Communications · doi:10.1038/s41467-017-00505-8 · Cited by 185 · see citing works
Biomaterials for mRNA delivery
Islam, M. A., Reesor, E. K. G., Xu, Y., Zope, H. R., Zetter, B. R., & Shi, J. (2015) · Biomaterials Science · doi:10.1039/c5bm00198f · Cited by 176 · see citing works
Parry, R. V., Rumbley, C. A., Vandenberghe, L. H., June, C. H., & Riley, J. L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.166 · Cited by 169 · see citing works
Self-citationTasian, S. K., Kenderian, S. S., Shen, F., Ruella, M., Shestova, O. E., Kozlowski, M. S., Li, Y., Schrank-Hacker, A. M., Morrissette, J. J. D., Carroll, M. P., et al. (2017) · Blood · doi:10.1182/blood-2016-08-736041 · Cited by 167 · see citing works
Self-citationMicroRNAs Enable mRNA Therapeutics to Selectively Program Cancer Cells to Self-Destruct
Jain, R., Frederick, J. P., Huang, E. Y., Burke, K. E., Mauger, D. M., Andrianova, E. A., Farlow, S. J., Siddiqui, S., Pimentel, J., Cheung-Ong, K., et al. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0734 · Cited by 164 · see citing works
Alnylam launches era of RNAi drugs
Garber, K. (2018) · Nature Biotechnology · doi:10.1038/nbt0918-777 · Cited by 159 · see citing works
Constrained Nanoparticles Deliver siRNA and sgRNA to T Cells In Vivo without Targeting Ligands
Lokugamage, M. P., Sago, C. D., Gan, Z., Krupczak, B. R., & Dahlman, J. E. (2019) · Advanced Materials · doi:10.1002/adma.201902251 · Cited by 155 · see citing works
Granot-Matok, Y., & Peer, D. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.08.015 · Cited by 154 · see citing works
Nanoparticles for nucleic acid delivery: Applications in cancer immunotherapy
Mukalel, A. J., Riley, R., Zhang, R., & Mitchell, M. J. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.040 · Cited by 140 · see citing works
Self-citationThe market for chimeric antigen receptor T cell therapies
Yip, A., & Webster, R. M. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.266 · Cited by 137 · see citing works
Foster, J., Choudhari, N., Perazzelli, J., Storm, J., Hofmann, T. J., Jain, P., Storm, P. B., Pardi, N., Weissman, D., Waanders, A. J., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.145 · Cited by 133 · see citing works
Castellà, M., Boronat, A., Martín‐Ibáñez, R., Rodríguez, V., Suñé, G., Caballero‐Baños, M., Marzal, B., Pérez-Amill, L., Martín-Antonio, B., Castaño, J., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.11.010 · Cited by 126 · see citing works
Engineered T cells for cancer therapy
June, C. H., Maus, M. V., Plesa, G., Johnson, L. A., Zhao, Y., Levine, B. L., Grupp, S. A., & Porter, D. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1568-1 · Cited by 124 · see citing works
Self-citationHarrer, D. C., Simon, B., Fujii, S., Shimizu, K., Uslu, U., Schuler, G., Gerer, K. F., Hoyer, S., Dörrie, J., & Schaft, N. (2017) · BMC Cancer · doi:10.1186/s12885-017-3539-3 · Cited by 121 · see citing works
Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines
Démoulins, T., Milona, P., Englezou, P. C., Ebensen, T., Schulze, K., Suter, R., Pichon, C., Midoux, P., Guzmán, C. A., Ruggli, N., et al. (2015) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2015.11.001 · Cited by 107 · see citing works
Cationic lipid-assisted nanoparticles for delivery of mRNA cancer vaccine
Fan, Y.-N., Li, M., Luo, Y., Chen, Q., Wang, L., Zhang, H., Shen, S., Gu, Z., & Wang, J. (2018) · Biomaterials Science · doi:10.1039/c8bm00908b · Cited by 105 · see citing works
Yoon, S. H., Lee, J. M., Cho, H. I., Kim, E. K., Kim, H. S., Park, M. Y., & Kim, T. (2008) · Cancer Gene Therapy · doi:10.1038/cgt.2008.98 · Cited by 102 · see citing works
The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy
Foster, J., Barrett, D. M., & Karikó, K. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.018 · Cited by 98 · see citing works
mRNA Delivery System for Targeting Antigen‐Presenting Cells In Vivo
Fornaguera, C., Guerra‐Rebollo, M., Lázaro, M. Á., Castells‐Sala, C., Meca‐Cortés, Ó., Ramos‐Pérez, V., Cascante, A., Rubio, N., Blanco, J., & Borrós, S. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201800335 · Cited by 95 · see citing works
Dullaers, M., Breckpot, K., Meirvenne, S. V., et al. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.07.017 · Cited by 91 · see citing works
Nonviral RNA chimeric antigen receptor–modified T cells in patients with Hodgkin lymphoma
Svoboda, J., Rheingold, S. R., Gill, S. I., et al. (2018) · Blood · doi:10.1182/blood-2018-03-837609 · Cited by 84 · see citing works
Structurally Programmed Assembly of Translation Initiation Nanoplex for Superior mRNA Delivery
Li, J., Wang, W., He, Y., Li, Y., Yan, E. Z., Zhang, K., Irvine, D. J., & Hammond, P. T. (2017) · ACS Nano · doi:10.1021/acsnano.6b08447 · Cited by 82 · see citing works
Liu, Y., Chen, X., Han, W., et al. (2017) · Drugs of today · doi:10.1358/dot.2017.53.11.2725754 · Cited by 78 · see citing works
Singh, N., Liu, X., Hulitt, J., Jiang, S., June, C. H., Grupp, S. A., Barrett, D. M., & Zhao, Y. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0051 · Cited by 77 · see citing works
Self-citationSynthetic Messenger RNA as a Tool for Gene Therapy
Rabinovich, P. M., Komarovskaya, M., Ye, Z.-J., Imai, C., Campana, D., Bahceci, E., & Weissman, S. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.1027 · Cited by 73 · see citing works
Heslop, H. E. (2010) · Molecular Therapy · doi:10.1038/mt.2010.42 · Cited by 70 · see citing works
RNA-based gene transfer for adult stem cells and T cells
Smits, E., Ponsaerts, P., Lenjou, M., Nijs, G., van Bockstaele, D. V., Berneman, Z., & Tendeloo, V. V. (2004) · Leukemia · doi:10.1038/sj.leu.2403463 · Cited by 67 · see citing works
Berdeja, J. G., Lin, Y., Raje, N. S., Siegel, D. S. D., Munshi, N. C., Liedtke, M., Jagannath, S., Maus, M. V., Turka, A., Lam, L. P., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.3010 · Cited by 57 · see citing works
Nanoparticulate systems for polynucleotide delivery.
Basarkar, A., & Singh, J. (2007) · PubMed · Cited by 54 · see citing works
Zhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la201464k · Cited by 48 · see citing works
An, N., Tao, Z., Li, S., Xing, H., Tang, K., Tian, Z., Rao, Q., Wang, M., & Wang, J. (2016) · Oncotarget · doi:10.18632/oncotarget.7079 · Cited by 42 · see citing works
Büning, H., Uckert, W., Cichutek, K., et al. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.131 · Cited by 31 · see citing works
Electroporation for Gene Therapy
Matthews, K. E., Dev, S. B., Toneguzzo, F., et al. (2003) · Humana Press eBooks · doi:10.1385/0-89603-304-x:273 · Cited by 20 · see citing works
Elusive Neurotoxicity in T Cell-Boosting Anticancer Therapies
Zheng, P., Kros, J. M., & Wang, G. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.02.005 · Cited by 11 · see citing works
Hartsell, A. (2019) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2018.12.544 · Cited by 6 · see citing works
Synthetic Messenger RNA as a Tool for Gene Therapy
Rabinovich, P. M., Komarovskaya, M. E., Ye, Z., et al. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.ft-249 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [17]Yang G; Sau C; Lai W; Cichon J; Li W The Principles of Engineering Immune Cells to Treat Cancer Wendell. Cell 2015, 344 (6188), 1173– 1178.
- [44]Singh N; Liu X; Hulitt J; Jiang S; June CH; Grupp SA; Barrett DM; Zhao Y Nature of Tumor Control by Permanently and Transiently Modified GD2 Chimeric Antigen Receptor T Cells in Xenograft Models of Neuroblastoma. Cancer Immunol. Res 2014, 2 (11), 1059– 1070. 25104548 PMC5584373
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Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., Zhou, X., Sharf-Pauker, N., Xiao, Y., Adir, O., Liang, H., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00104-y · Cited by 719 · see citing works
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Liu, C., Shi, Q., Huang, X., Koo, S., Kong, N., & Tao, W. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-023-00586-2 · Cited by 500 · see citing works
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Zhou, J.-E., Sun, L., Liu, L., Jia, Y., Han, Y., Shao, J., Wang, J., Wang, Y., Yu, L., & Yan, Z. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.01.038 · Cited by 104 · see citing works
Han, E. L., Padilla, M. S., Palanki, R., Kim, D., Mrksich, K., Li, J. J., Tang, S., Yoon, I.-C., & Mitchell, M. J. (2024) · Nano Letters · doi:10.1021/acs.nanolett.3c03509 · Cited by 72 · see citing works
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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
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Kairuz, D., Samudh, N., Ely, A., Arbuthnot, P., & Bloom, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1018961 · Cited by 25 · see citing works
Han, E. L., Kim, D., Murray, A. M., Mrksich, K., Hamilton, A. G., Tang, S., Yoo, S., Zhu, A. T., Tong, E. R., Palanki, R., et al. (2026) · ACS Nano · doi:10.1021/acsnano.5c19138 · Cited by 5 · see citing works
Self-citation
- Authors
- Billingsley, M. M., Singh, N., Ravikumar, P., Zhang, R., June, C. H., & Mitchell, M. J.
- Affiliations
- University of Pennsylvania (US)
- Washington University in St. Louis (US)
- Abramson Cancer Center (US)
- Corresponding author
- Mitchell, Michael J.
- ORCID
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-01-17
- Volume
- 20
- Issue
- 3
- Pages
- 1578-1589
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- PMC
- PMC7313236
- OpenAlex
- W2999972782
- Cited by
- 636
- References
- 93
- Citations by year
- 2026: 108 · 2025: 111 · 2024: 133 · 2023: 94 · 2022: 97 · 2021: 61 · 2020: 29 · 2019: 2
- FWCI
- 22.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Advancing Translational Sciences (DP2TR002776)
- American Association for Cancer Research (18-80-44-MITC)
- National Cancer Institute (P30 CA016520, R01 CA241661)
- American Cancer Society (129784-IRG-16-188-38-IRG)
- Burroughs Wellcome Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- ionizable lipid nanoparticles, mRNA delivery, chimeric antigen receptor T cells, CAR-T cell engineering, electroporation, Jurkat cells, acute lymphoblastic leukemia, B-cell lymphoma, viral vector alternatives, cytotoxicity
- MeSH terms
- Receptors, Chimeric Antigen, Humans, Lipids, RNA, Messenger, T-Lymphocytes, Drug Delivery Systems, Coculture Techniques, Cell Line, Tumor, Nanoparticles, Cell Engineering
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