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Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer
Open accessAbstract
Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus.
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“Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications.”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [71]
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Citations
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Kishimoto, T. (1989) · Blood · doi:10.1182/blood.v74.1.1.bloodjournal7411 · Cited by 2,068
Improved retroviral vectors for gene transfer and expression.
Miller, A. D., & Rosman, G. J. (1989) · PubMed · Cited by 1,990
Mann, R., Mulligan, R. C., & Baltimore, D. (1983) · Cell · doi:10.1016/0092-8674(83)90344-6 · Cited by 1,776
Miller, A. D., & Buttimore, C. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.8.2895-2902.1986 · Cited by 1,371
Granulocyte colony-stimulating factor and its receptor
Demetri, G. D., & Griffin, J. D. (1991) · Blood · doi:10.1182/blood.v78.11.2791.2791 · Cited by 1,066
A safe packaging line for gene transfer: separating viral genes on two different plasmids
Markowitz, D., Goff, S. P., & Bank, A. (1988) · Journal of Virology · doi:10.1128/jvi.62.4.1120-1124.1988 · Cited by 1,062
Danos, O., & Mulligan, R. C. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.17.6460 · Cited by 898
Yang, Y., Ciarletta, A. B., Temple, P. A., Chung, M. P., Kovacic, S., Witek-Giannotti, J. S., Leary, A. C., Kriz, R., Donahue, R. E., Wong, G. G., et al. (1986) · Cell · doi:10.1016/0092-8674(86)90360-0 · Cited by 766
Self-citationPrimary structure and functional expression of rat and human stem cell factor DNAs
Martin, F. H., Suggs, S. V., Langley, K. E., Lu, H. S., Ting, J., Okino, K. H., Morris, C. F., McNiece, I., Jacobsen, F. W., Mendlaz, E. A., et al. (1990) · Cell · doi:10.1016/0092-8674(90)90301-t · Cited by 719
Construction and use of a safe and efficient amphotropic packaging cell line
Markowitz, D., Goff, S. P., & Bank, A. (1988) · Virology · doi:10.1016/0042-6822(88)90101-8 · Cited by 670
Molecular physiology of granulocyte-macrophage colony-stimulating factor
Gasson, J. C. (1991) · Blood · doi:10.1182/blood.v77.6.1131.bloodjournal7761131 · Cited by 654
Miller, A. D. (1990) · Human Gene Therapy · doi:10.1089/hum.1990.1.1-5 · Cited by 382
Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells
Kirshenbaum, A. S., Kessler, S., Goff, J. P., & Metcalfe, D. D. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.5.1410 · Cited by 361
Self-citationRapid Cell Culture Assay Technique for Murine Leukaemia Viruses
Bassin, R. H., TUTTLE, N., & Fischinger, P. J. (1971) · Nature · doi:10.1038/229564b0 · Cited by 358
Kirshenbaum, A. S., Goff, J. P., Kessler, S., Mican, J. M., Zsebo, K. M., & Metcalfe, D. D. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.3.772 · Cited by 284
Self-citationTreatment of genetic defects in hematopoietic cell function by gene transfer
Karlsson, S. (1991) · Blood · doi:10.1182/blood.v78.10.2481.2481 · Cited by 212
Krantz, S. B. (1991) · PubMed · Cited by 206
Safety Issues Related to Retroviral-Mediated Gene Transfer in Humans
Cornetta, K. G., Morgan, R. A., & Anderson, W. F. (1991) · Human Gene Therapy · doi:10.1089/hum.1991.2.1-5 · Cited by 201
Kantoff, P. W., Gillio, A. P., McLachlin, J. R., Bordignon, C., Eglitis, M. A., Kernan, N. A., Moen, R. C., Kohn, D. B., Yu, S. F., & Karson, E. M. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.166.1.219 · Cited by 176
Self-citationBodine, D. M., McDonagh, K. T., Brandt, S. J., Ney, P. A., Agricola, B. A., Byrne, E. R., & Nienhuis, A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3738 · Cited by 175
Self-citationNienhuis, A. W., Donahue, R. E., Karlsson, S., Clark, S., Agricola, B. A., Antinoff, N., Pierce, J. E., Turner, P. L., Anderson, W. F., & Nathan, D. G. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113106 · Cited by 169
Self-citationEvans, L. H., Morrison, R. P., Malik, F., Portis, J. L., & Britt, W. J. (1990) · Journal of Virology · doi:10.1128/jvi.64.12.6176-6183.1990 · Cited by 164
Retroviral RNA Packaging: Sequence Requirements and Implications
Linial, M., & Miller, A. D. (1990) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-75218-6_5 · Cited by 155
Amphotropic Murine Leukemia Retrovirus Is Not an Acute Pathogen for Primates
Cornetta, K. G., Moen, R. C., Culver, K. W., Morgan, R. A., McLachlin, J. R., Sturm, S., Selegue, J. E., London, W. T., Blaese, R. M., & Anderson, W. F. (1990) · Human Gene Therapy · doi:10.1089/hum.1990.1.1-15 · Cited by 146
Self-citationMoore, K. A., Deisseroth, A., Reading, C., Williams, D. E., & Belmont, J. (1992) · Blood · doi:10.1182/blood.v79.6.1393.1393 · Cited by 142
Culver, K. W., Anderson, W. F., & Blaese, R. M. (1991) · Human Gene Therapy · doi:10.1089/hum.1991.2.2-107 · Cited by 128
Carter, R., Abrams-Ogg, A., Dick, J. E., Kruth, S. A., Valli, V. E., Kamel‐Reid, S., & Dube, I. (1992) · Blood · doi:10.1182/blood.v79.2.356.356 · Cited by 122
Evolutionary implications of primate endogenous retroviruses
Shih, A., Coutavas, E. E., & Rush, M. G. (1991) · Virology · doi:10.1016/0042-6822(91)90590-8 · Cited by 88
Retrovirus-mediated gene transduction into long-term repopulating marrow cells of dogs
Schuening, F., Kawahara, K., Miller, A. D., To, R., Goehle, S., Stewart, D., Mullally, K., Fisher, L. D., Graham, T., & Appelbaum, F. R. (1991) · Blood · doi:10.1182/blood.v78.10.2568.bloodjournal78102568 · Cited by 86
Detection of receptor-specific murine leukemia virus binding to cells by immunofluorescence analysis
Kadan, M. J., Sturm, S., Anderson, W. F., & Eglitis, M. A. (1992) · Journal of Virology · doi:10.1128/jvi.66.4.2281-2287.1992 · Cited by 74
Cornetta, K. G., Ra, M., Gillio, A. P., Sturm, S., Baltrucki, L., & O’reilly, R. J. (1991) · Human Gene Therapy · doi:10.1089/hum.1991.2.3-215 · Cited by 74
Murine Leukemia Viruses with Recombinant env Genes: A Discussion of Their Role in Leukemogenesis
Famulari, N. G. (1983) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-68943-7_4 · Cited by 71
Virus-Host Interactions and the Pathogenesis of Murine and Human Oncogenic Retroviruses
Tsichlis, P. N., & Lazo, P. A. (1991) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-76524-7_5 · Cited by 69
Analysis of retroviral packaging lines for generation of replication-competent virus
Muenchau, D. D., Freeman, S. M., Cornetta, K. G., Zwiebel, J. A., & Anderson, W. F. (1990) · Virology · doi:10.1016/0042-6822(90)90251-l · Cited by 65
Gene transfer into hematopoietic stem cells
Nienhuis, A. W., McDonagh, K. T., & Bodine, D. M. (1991) · Cancer · doi:10.1002/1097-0142(19910515)67:10+ · Cited by 47
Self-citationDaley, J. P., Rozans, M. K., Br, S., Burakoff, S. J., Rappeport, J., & Miller, R. A. (1987) · Blood · doi:10.1182/blood.v70.4.960.960 · Cited by 44
Tsichlis, P. N., & Bear, S. E. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.11.4611 · Cited by 29
Oncogenesis by Moloney murine leukemia virus.
Pn, T. (1987) · PubMed · Cited by 29
Wieder, R., Cornetta, K. G., Kessler, S., & Anderson, W. (1991) · Blood · doi:10.1182/blood.v77.3.448.448 · Cited by 27
Self-citationThe influence of radiation therapy on T-lymphocyte subpopulations defined by monoclonal antibodies
Job, G., Pfreundschuh, M. G., Bauer, M., Winkel, K. Z., & HUNSTEIN, W. (1984) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(84)90205-0 · Cited by 22
Detection of simian T‐lymphotropic virus type I using the polymerase chain reaction
Dezzutti, C. S., Lazo, A., Yee, J. Y., Blakeslee, J. R., Mathes, L. E., Brown, B. G., & Lairmore, M. D. (1992) · International Journal of Cancer · doi:10.1002/ijc.2910500524 · Cited by 10
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LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1
Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P., Lim, A., Osborne, C. S., Pawliuk, R., Morillon, E., et al. (2003) · Science · doi:10.1126/science.1088547 · Cited by 3,587
The Basic Science of Gene Therapy
Mulligan, R. C. (1993) · Science · doi:10.1126/science.8493530 · Cited by 1,741
Infection of human cells by an endogenous retrovirus of pigs
Patience, C., Takeuchi, Y., & Weiss, R. A. (1997) · Nature Medicine · doi:10.1038/nm0397-282 · Cited by 953
Polyethylenimine-based non-viral gene delivery systems
Lungwitz, U., Breunig, M., Blunk, T., & Göpferich, A. M. (2005) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2004.11.011 · Cited by 998
Biodegradable polymers as non-viral carriers for plasmid DNA delivery
Luten, J., van Nostrum, C. F., Smedt, S. C. D., & Hennink, W. E. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.10.028 · Cited by 475
Metadata
- Authors
- Donahue, R. E., Kessler, S. W., Bodine, D., McDonagh, K., Dunbar, C., Goodman, S., Agricola, B., Byrne, E., Raffeld, M., & Moen, R.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1992-10-01
- Volume
- 176
- Issue
- 4
- Pages
- 1125-1135
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2119385
- OpenAlex
- W2132859839
- Cited by
- 532
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2022: 8 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 10 · 2017: 7 · 2015: 8 · 2014: 11 · 2013: 5 · 2012: 9
- FWCI
- 17.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Keywords
- Moloney murine leukemia virus, retroviral vectors, replication-competent virus, T-cell lymphoma, helper virus, retroviral gene transfer, CD34+ hematopoietic stem cells, bone marrow transplantation, rhesus monkeys, non-human primates, gene therapy safety, thymic lymphoma
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigens, Differentiation, Base Sequence, Cells, Cultured, DNA, Neoplasm, DNA, Viral, Globins, Helper Viruses, Macaca mulatta, Molecular Sequence Data, Moloney murine leukemia virus, Oligodeoxyribonucleotides, Time Factors, Transfection, Virus Replication, Antigens, CD, Bone Marrow Transplantation, Lymphoma, T-Cell, Genome, Viral, Antigens, CD34
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