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Development of CAR T-cell lymphoma in 2 of 10 patients effectively treated with piggyBac-modified CD19 CAR T cells
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“Further, in a recent phase I trial, lymphoma arising from piggyBac transfected CAR T cells has been reported in two of nine patients with relapsed or refractory B-cell malignancies who achieved complete remission after product infusion.”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [107]
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Citations
Cites
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
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CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
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Cited by
Sorted by citations
Items 101–150 of 150
van Hees, E. P., Morton, L. T., Remst, D., Wouters, A., Eynde, A. V. D., Falkenburg, J. F. F., & Heemskerk, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1368290 · Cited by 6
Gottlieb, D., Sutrave, G., Jiang, W., Avdic, S., Street, J., Simms, R., Clancy, L., Antonenas, V., Gloss, B., Bateman, C., et al. (2022) · American journal of hematology/oncology · doi:10.1002/ajh.26594 · Cited by 6
“A unit of steady-state donor peripheral blood was collected prior to transplant, and using a PiggyBac transposon transposase system, a CD19 CAR expressing T-cell product was generated as previously described.(7) In both cases, HLA-matched sibling donors underwent G-CSF mobilized peripheral blood stem cell collection a…”
MethodSelf-citationCharacterizing piggyBat—a transposase for genetic modification of T cells
Sutrave, G., Xu, N., Tang, T. C. Y., Dolnikov, A., Gloss, B., Gottlieb, D., Micklethwaite, K., & Gowrishankar, K. (2022) · Molecular Therapy: Methods & Clinical Development · doi:10.1016/j.omtm.2022.03.012 · Cited by 6
Self-citationOrmhøj, M., Abken, H., & Hadrup, S. R. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03163-y · Cited by 9
Peripheral T cell lymphoma following CD19-targeted chimeric antigen receptor T cell therapy
Tatetsu, H., Kato, K., Wada, A., Hirano, T., Ueno, S., Miyasato, Y., Yamada, A., Shichijo, T., Higuchi, Y., Ueda, Y., et al. (2025) · International journal of hematology · doi:10.1007/s12185-025-04074-1 · Cited by 5
Anagnostopoulos, I., Lakić, T., Balagué, O., van den Brand, M., Dirnhofer, S., Gašljević, G., Laurent, C., Ponzoni, M., Quintanilla‐Martínez, L., Sander, B., et al. (2025) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-025-04197-0 · Cited by 6
Non-viral vectors for chimeric antigen receptor immunotherapy
Tretbar, S., Rurik, J. G., Rustad, E. H., Sürün, D., Koehl, U., Olweus, J., Buchholz, F., Ivics, Z., Fricke, S., & Blache, U. (2024) · Nature Reviews Methods Primers · doi:10.1038/s43586-024-00348-w · Cited by 15
On the road to in vivo CAR-T success: Comparing promising viral and non-viral vectors
de la Mota, S., Suchet, L., van Wijk, M., Stibbs, D. J., Couto, P. S., & Rafiq, Q. A. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.108907 · Cited by 6
Biomarker-empowered precision navigation of CAR-T cell therapy
Wang, Y., Cheng, W., Kang, K., Niu, T., Zhao, A., & Wu, Y. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02647-0 · Cited by 5
Tîrziu, A., Bojin, F. M., Gavriliuc, O. I., Faur, C. I., & Păunescu, V. (2025) · Cells · doi:10.3390/cells15010070 · Cited by 3
“…trials using SB transposons have demonstrated >90% CAR-positive rates with favorable safety profiles without evidence of genotoxicity or malignant transformation [55], though the CARTELL trial reported lymphoma development in 2/10 patients, potentially linked to multiple integration events [56].”
A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy
Maurer, K., Weir, J. A., Nagler, A., Haradhvala, N., Bharadwaj, H., Shapiro, J., Alakwe, S., Kumar, V., Waller, B. F., McDonough, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62709-7 · Cited by 4
“The majority of these do not appear to result from malignant transformation from CAR-T insertional mutagenesis 7,9,10 .”
Maurer, K., & Jacobson, C. (2025) · Leukemia and Lymphoma · doi:10.1080/10428194.2025.2460043 · Cited by 4
“However, a phase i clinical trial of cD19-directed cAR-t cells generated using the PiggyBac transposon system resulted in two out of 10 total patients developing cAR-t cell-derived lymphoma [38].”
Ligon, J. A., Ramakrishna, S., Ceppi, F., Calkoen, F., Diorio, C. J., Davis, K. L., Jacoby, E., Gottschalk, S. M., Schultz, L. M., & Capitini, C. M. (2023) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2023.10.012 · Cited by 4
The road ahead for chimeric antigen receptor T cells
Stewart, C. M., Siegler, E. L., & Kenderian, S. S. (2025) · The Journal of Immunology · doi:10.1093/jimmun/vkaf047 · Cited by 4
Rajput, A., Sajjad, S. A., Kumar, A., & Singh, K. (2025) · Cureus · doi:10.7759/cureus.81930 · Cited by 3
“In all the studies, CAR gene delivery was carried out using the SB transposon system except for one study that used the PB transposon system [15].”
Pharmacological control of CAR T cells through CRISPR-driven rapamycin resistancePreprint
Levesque, S., Carleton, G. A., Duque, V., Goupil, C., Fiset, J.-P., Villeneuve, S., Normandeau, É., Morin, G., Dumont, N., Nelson, B. H., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.14.557485 · Cited by 4
“However, delivery of this large transgene is limiting, and product-derived lymphomas have been reported with piggyBac -modified CAR-T cells 28,29 , so editing the endogenous MTOR locus to generate dominant cellular resistance to rapamycin using CRISPR could be a viable alternative.”
BackgroundExploration of the potential of genomic editing in the treatment of congenital adrenal hyperplasia
Graves, L. E., Christina, S., Mullany, K., Alexander, I. E., & Falhammar, H. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1719376 · Cited by 2
Šmilauerová, K., Štach, M., Mucha, M., Vaníková, Š., Rychlá, J., & Otáhal, P. (2024) · Immunotherapy Advances · doi:10.1093/immadv/ltaf022 · Cited by 2
“Similarly, the genotoxicity of piggyBac transposon was also reported [39, 40].”
Libertini, S., Jadlowsky, J. K., Lanz, T. A., Mihalcik, L., & Pizzurro, D. M. (2024) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22633 · Cited by 2
“Although the pathogenic mechanism remains undefined, the investigators postulate that the malignant transformation is likely a result of multiple genetic alterations (Bishop et al., 2021; Micklethwaite et al., 2021).”
Sheedy, A. M., Burduli, N., Prakash, A., Gurney, M., Hanley, S., Prendeville, H., Sarkar, S., O'Dwyer, J., O'Dwyer, M., & Dolan, E. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34976 · Cited by 2
CAR T cell resistance to oncogenic transformation.
Ruella, M., & June, C. H. (2024) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-23-0273 · Cited by 2
“In both cases, the post-CART TCL progressed and resulted in the death of one of the patients, whereas the other patient successfully received an allogeneic transplant (6).”
Laoharawee, K., Kleinboehl, E. W., Jensen, J. D., Peterson, J. J., Slipek, N. J., Wick, B., Johnson, M. J., Webber, B. R., & Moriarity, B. (2024) · bioRxiv · doi:10.1101/2024.04.23.590790 · Cited by 2
“54,55 Despite this, studies using lentivirus and transpons to engineer Tm cells for the production of therapeutic proteins have shown great promise.”
BackgroundAre we ready for personalized CAR‐T therapy?
Strzelec, A., & Helbig, G. (2023) · European Journal Of Haematology · doi:10.1111/ejh.14039 · Cited by 3
“Allogeneic anti-CD19 CAR-T, obtained from HLA-compatible siblings from whose cells were collected for a previously unsuccessful allo-HSCT, using piggyBac, was applied by Bishop et al. 78 ; however, CAR19 T-cell lymphoma occurred in 2 of 10 patients.”
MethodA comprehensive review of T-cell lymphoma following CAR T-cell immunotherapy
Shi, W.-P. J., & Wang, H.-Y. (2026) · Blood Advances · doi:10.1182/bloodadvances.2026021166 · Cited by 2
“One patient died within 21 days from hemophagocytic lymphohistiocytosis associated with an ALK + ALCL, 37 whereas others had an indolent clinical course, 43,48,49 similar to that of recently described indolent TCL (ITCL) of the GI tract.”
CAR-NK cell therapy for hematological malignancies
Manzar, G. S., Hasan, M. F., Moore, M., Tiberti, S., Başar, R., & Daher, M. (2026) · Blood Advances · doi:10.1182/bloodadvances.2024014082 · Cited by 2
“62 Newer methods in CAR-NK cell generation combined minicircle DNA and a Sleeping Beauty transposase system, demonstrating preferential integration into safer genomic harbors, with robust antitumor activity.”
Guerreiro, M. C., Pinto, I. S., Farinha, D., & Faneca, H. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.126848 · Cited by 1
T cell lymphomas: cancers of aberrant immune synapse signalling
Tauber, P. A., & Ruland, J. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01283-5 · Cited by 1
“there have been recent reports of T cell lymphomas arising from chimeric antigen receptor (CAR) T cells that were engineered and infused into patients to treat other malignancies but subsequently underwent malignant transformation 6–9 .”
Liu, X., Gao, H., & Yu, J. (2026) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbag007
“However, viral vector-based approaches carry a potential risk of insertional mutagenesis due to random genomic integration, and cases of malignant transformation have been re-ported in some CAR-T cell treatments [ 43–46 ].”
Genetic Engineering Methods in Primary T Cells
Youssef, A., & Li, H.-S. (2025) · Advanced Therapeutics · doi:10.1002/adtp.202500149
Safety of genetically modified T cells.
Maus, M. V. (2022) · Blood · doi:10.1182/blood.2022016334 · Cited by 1
New indications and platforms for CAR‐T therapy in lymphomas beyond DLBCL
Iqbal, M., Savani, B. N., & Hamadani, M. (2021) · eJHaem · doi:10.1002/jha2.323 · Cited by 2
“generated anti-CD19CAR-T fromHLA-identical sibling donors of allo-transplant recipients with relapsed B-cell acute leukemia or highgrade NHL, using the high-capacity piggyBac transposon, instead of a viral vector [95].”
Beyond Viruses: Transposons and CRISPR-Programmable Nonviral Systems for Genome Engineering.
Singh, S., Panchal, O., & Ivics, Z. (2026) · Human Gene Therapy · doi:10.1177/10430342261493722
T-cell lymphoma following chimeric antigen receptor-T therapy: a cause for concern?
Stella, F., Fraietta, J., Schuster, S., & Ruella, M. (2026) · Haematologica · doi:10.3324/haematol.2026.301592
“…transposon-engineered CAR T cells, in which CAR-expressing T-cell lymphomas showed high transgene copy numbers and complex genomic alterations 52 , highlighting that transgene copy number, genomic instability, and clonal selection may matter at least as much as the identity of the…”
A review of genetic modification for ex vivo cellular therapies
Dinh, A., Zhang, N., & Stroncek, D. F. (2026) · Transfusion · doi:10.1111/trf.70163
“68 Thus far, there have been two cases of posttreatment lymphoma after piggyBac-transposed CAR-T treatment for non-Hodgkin lymphoma, with no reported cases for SB. 71 Compared to viral vectors, transposon-based approaches have higher cargo capacities (up to (cid”
Managing Novel CAR T-Cell Toxicities in Multiple Myeloma.
Ang, K.-K., Lipof, J. J., Kumar, A., Mikkilineni, L., Chung, A., Arora, S., Sayre, P. H., Wolf, J., Chari, A., Martin, T. G., et al. (2026) · Cancer Journal · doi:10.1097/ppo.0000000000000849
Chimeric Antigen Receptor-T Cells Fate after Infusion: Cellular Kinetics and Molecular Monitoring
Anelli, L., Cumbo, C., Minervini, A., Zagaria, A., Coccaro, N., Tarantini, F., Tota, G., Conserva, M. R., Redavid, I., Minervini, C. F., et al. (2026) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2026.06.041
Andrade, C. D. O., Bezerra, M. R. L., Sousa, I. G., Correia, E. M., Lima, A. J. F., Abdo, L. D. M., Aragão, E. A. A., Araújo, R. P. D. S., Pinheiro, D. P., Studart, I. C., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1798748 · Cited by 1
Park, J. J., Avigan, Z. M., Dong, M. B., Nguyen, C. V., Guitart, J., Kotecha, R., Perica, K., Parekh, S., & Aleman, A. (2026) · Blood neoplasia · doi:10.1016/j.bneo.2026.100244
CAR-T and CAR-NK therapies in pediatric oncology: opportunities and challenges
Abbasova, F., Alieva, R., Kitalaev, K. Z., & Polyakova, O. V. (2026) · Russian Journal of Pediatric Hematology and Oncology · doi:10.21682/2311-1267-2026-13-1-60-68
Unveiling genomic rearrangements in engineered iPSC lines by optical genome mapping
Finlay, D., Hor, P., Goldenson, B., Li, X., Murad, R., Kaufman, D. S., & Vuori, K. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101644
嵌合抗原受体T细胞与嵌合抗原受体调节性T细胞在自身免疫性疾病治疗中的研究进展
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Identification of clonally expanded γδ T‐cell populations during CAR‐T cell therapy
Safavi, A., Samir, J., Singh, M., Bonomi, M., Louie, R. H. Y., Micklethwaite, K. P., & Luciani, F. (2024) · Immunology and Cell Biology · doi:10.1111/imcb.12834 · Cited by 1
“Patients P2 and P8 developed CAR-T cell induced lymphoma at 3.2-and 11.5-months following therapy, respectively 15,16 (Table 1).”
InfluentialSelf-citationA retrotransposon for site-specific gene transfer
Dyda, F., & Hickman, A. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02180-9
Tanaka, M., Iwamoto, Y., Wang, B., Imai, E., Yoshida, M., Iriguchi, S., & Kaneko, S. (2024) · Regenerative Therapy · doi:10.1016/j.reth.2024.03.002
“Since the mechanism are still unclear, it was concluded that follow-up is important [37].”
BackgroundClinical application of cell‐based therapies opportunities and challenges
Gao, J., & Wu, D. (2022) · Clinical and Translational Discovery · doi:10.1002/ctd2.110
(2022) · Reactions weekly · doi:10.1007/s40278-022-25847-0
Bonamino, M., Paiva, R. M. A., de Godoy, J. A. P., Kondo, A. T., Okamoto, O. K., & Kerbauy, L. N. (2022) · JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY · doi:10.46765/2675-374x.2022v3n1p155
Louie, R. H. Y., Cai, C., Singh, M., Deveson, I. W., Ferguson, J. M., Amos, T. G., McGuire, H. M., Samir, J., Gowrishankar, K., Adikari, T. N., et al. (2022) · medRxiv · doi:10.1101/2022.03.29.22273013
Self-citationEin Streifzug durch ausgewählte Themen der Kinder-Onkologie und -Hämatologie
Borkhardt, A. (2022) · Kinder- und Jugendmedizin · doi:10.1055/a-1664-5825
Allogeneic Hematopoietic Cell Transplantation and Cellular Therapy
Kim, H.-J., Weisdorf, D. J., & Gottlieb, D. (2021) · Blood cell therapy · doi:10.31547/bct-2021-014
Self-citation
Metadata
- Authors
- Bishop, D. C., Clancy, L. E., Simms, R., Burgess, J., Mathew, G., Moezzi, L., Street, J. A., Sutrave, G., Atkins, E., McGuire, H. M., Gloss, B. S., Lee, K., Jiang, W., Maddock, K., McCaughan, G., Avdic, S., Antonenas, V., O’Brien, T. A., Shaw, P. J., Irving, D. O., Gottlieb, D. J., Blyth, E., & Micklethwaite, K. P.
- Affiliations
- The University of Sydney (AU)
- Westmead Institute for Medical Research (AU)
- Westmead Hospital (AU)
- NSW Health Pathology (AU)
- Children’s Cancer Institute, Sydney, NSW, Australia;
- University of Technology Sydney (AU)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2021-10-21
- Volume
- 138
- Issue
- 16
- Pages
- 1504-1509
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W3160982226
- Cited by
- 177
- References
- 27
- Citations by year
- 2026: 20 · 2025: 35 · 2024: 45 · 2023: 31 · 2022: 29 · 2021: 17
- FWCI
- 11.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- David and Elaine Potter Foundation
- Ian Potter Foundation
- Cancer Australia (1047454)
- Cancer Institute NSW
- Cure Cancer Australia Foundation
- Medical Research Council
- National Health and Medical Research Council (1102172)
- Cancer Council NSW
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CAR T-cell therapy, piggyBac transposon, CD19, T-cell leukemia, B-cell acute lymphoblastic leukemia
- MeSH terms
- Adult, Aged, DNA Transposable Elements, Female, Humans, Lymphoma, Male, Middle Aged, Receptors, Antigen, T-Cell, Leukemia, B-Cell, Immunotherapy, Adoptive, Lymphoma, B-Cell, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Young Adult
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