Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers
Open accessAbstract
Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA–peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 × 103/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.
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Protocols have been developed to adoptively transfer CMV-specific CD8+ T cells to prevent viral reactivation in transplant recipients.
“The importance of T cells targeting CMV is emphasised by protocols that have been developed to adoptively transfer CMV-specific CD8+ T cells to prevent viral reactivation in transplant recipients (Cobbold et al. 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Cobbold et al. 2005
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- Authors
- Cobbold, M., Khan, N., Pourgheysari, B., Tauro, S., McDonald, D., Osman, H., Assenmacher, M., Billingham, L., Steward, C., Crawley, C., Olavarria, E., Goldman, J., Chakraverty, R., Mahendra, P., Craddock, C., & Moss, P. A. H.
- Affiliations
- Cancer Research UK (GB)
- Queen Elizabeth Hospital Birmingham (GB)
- 4National Blood Transfusion Service, Birmingham B15 2SG, England, UK
- Miltenyi Biotec (Germany) (DE)
- Bristol Royal Hospital for Children (GB)
- Hammersmith Hospital (GB)
- 7Department of Haematology, Hammersmith Hospital, Imperial College, London W12 0HS, England, UK
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-08-01
- Volume
- 202
- Issue
- 3
- Pages
- 379-386
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2213070
- OpenAlex
- W2123440147
- Cited by
- 480
- References
- 21
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 5 · 2022: 16 · 2021: 11 · 2020: 15 · 2019: 18 · 2018: 20 · 2017: 21 · 2016: 22 · 2015: 37 · 2014: 30 · 2013: 28 · 2012: 38
- FWCI
- 18.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- cytomegalovirus, cytomegalovirus reactivation, adoptive T cell therapy, CMV-specific CD8+ T cells, stem cell transplantation, immunosuppression, viremia, refractory CMV infection
- MeSH terms
- Antigens, Viral, Cytomegalovirus Infections, Cytomegalovirus, Female, Hematologic Diseases, HLA Antigens, Humans, Male, Peptides, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Adoptive Transfer, Stem Cell Transplantation
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