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Schub, A. ; Schuster, I.G. ; Hammerschmidt, W. ; Moosmann, A.

CMV-specific TCR-transgenic T cells for immunotherapy.

J. Immunol. 183, 6819-6830 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Reactivation of CMV can cause severe disease after allogeneic hemopoietic stem cell transplantation. Adoptive T cell therapy was successfully used for patients who had received transplants from CMV-positive donors. However, patients with transplants from CMV-negative donors are at highest risk, and an adoptive therapy is missing because CMV-specific T cells are not available from such donors. To address this problem, we used retroviral transfer of CMV-specific TCR genes. We generated CMV-specific T cell clones of several HLA restrictions recognizing the endogenously processed Ag pp65. The genes of four TCRs were cloned and transferred to primary T cells from CMV-negative donors. These CMV-TCR-transgenic T cells displayed a broad spectrum of important effector functions (secretion of IFN-gamma and IL-2, cytotoxicity, proliferation) in response to endogenously processed pp65 and could be enriched and expanded by strictly Ag-specific stimulation. Expansion of engineered T cells was accompanied by an increase in specific effector functions, indicating that the transferred specificity is stable and fully functional. Hence, we expect these CMV-TCR-transgenic T cells to be effective in controlling acute CMV disease and establishing an antiviral memory.
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Publication type Article: Journal article
Document type Scientific Article
Keywords CD8-Positive T-Lymphocytes/ immunology; CD8-Positive T-Lymphocytes/transplantation; Clone Cells/immunology; Clone Cells/metabolism; Cytomegalovirus/immunology; Cytomegalovirus Infections/therapy; Cytotoxicity; Immunologic/immunology; Humans; Immunotherapy; Adoptive/methods; Interferon-gamma/immunology; Interferon-gamma/metabolism; Interleukin-2/immunology; Interleukin-2/metabolism; Phosphoproteins/immunology; Phosphoproteins/metabolism; Receptors; Antigen; T-Cell/genetics; Transduction; Genetic; Transgene
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Journal Journal of Immunology
Quellenangaben Volume: 183, Issue: 10, Pages: 6819-6830 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
CCG Molecular Oncology (AGV-KON)
Institute of Molecular Immunology (IMI)