Back to Search
Start Over
Effective treatment of refractory CMV reactivation after allogeneic stem cell transplantation with in vitro-generated CMV pp65-specific CD8+ T-cell lines.
- Source :
-
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2012 Oct; Vol. 35 (8), pp. 621-8. - Publication Year :
- 2012
-
Abstract
- To treat patients with refractory cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation, a phase I/II clinical study on adoptive transfer of in vitro-generated donor-derived or patient-derived CMV pp65-specific CD8* T-cell lines was performed. Peripheral blood mononuclear cells from CMV seropositive donors or patients were stimulated with HLA-A*0201-restricted and/or HLA-B*0702-restricted CMV pp65 peptides (NLV/TPR) and 1 day after stimulation interferon-γ)-producing cells were enriched using the CliniMACS Cytokine Capture System (interferon-γ), and cultured with autologous feeders and low-dose interluekin-2. After 7-14 days of culture, quality controls were performed and the CMV-specific T-cell lines were administered or cryopreserved. The T-cell lines generated contained 0.6-17 × 10(6) cells, comprising 54%-96% CMV pp65-specific CD8 T cells, and showed CMV-specific lysis of target cells. Fifteen CMV-specific T-cell lines were generated of which 8 were administered to patients with refractory CMV reactivation. After administration, no acute adverse events and no graft versus host disease were observed and CMV load disappeared. In several patients, a direct relation between administration of the T-cell line and the in vivo appearance of CMV pp65-specific T cells could be documented. In conclusion, administration of CMV pp65-specific CD8* T-cell lines was found to be feasible and safe, and enduring efficacy of administered CMV pp65-specific CD8* T-cell lines could be demonstrated.
- Subjects :
- CD8-Positive T-Lymphocytes transplantation
Cell Line
Cytotoxicity, Immunologic
HLA-A2 Antigen metabolism
HLA-B7 Antigen metabolism
Herpes Simplex etiology
Herpes Simplex immunology
Humans
Interferon-gamma metabolism
Interleukin-2 metabolism
Peptide Fragments immunology
Peptide Fragments metabolism
Phosphoproteins immunology
Phosphoproteins metabolism
Protein Binding
Transplantation, Homologous
Viral Load immunology
Viral Matrix Proteins immunology
Viral Matrix Proteins metabolism
Virus Activation
CD8-Positive T-Lymphocytes immunology
Herpes Simplex therapy
Immunotherapy, Adoptive methods
Postoperative Complications
Simplexvirus physiology
Stem Cell Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1537-4513
- Volume :
- 35
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy (Hagerstown, Md. : 1997)
- Publication Type :
- Academic Journal
- Accession number :
- 22996368
- Full Text :
- https://doi.org/10.1097/CJI.0b013e31826e35f6