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Open Access Green as soon as Postprint is submitted to ZB.
Efficient gene transfer of CD40 ligand into primary B-CLL cells using recombinant adeno- associated virus (rAAV) vectors.
Blood 100, 1655-1661 (2002)
B cells of chronic lymphocytic leukemia (B-CLL) are resistant to transduction with most currently available vector systems. Using an optimized adenovirus-free packaging system, recombinant adeno-associated virus (rAAV) vectors coding for the enhanced green fluorescent protein (AAV/EGFP) and CD40 ligand (AAV/CD40L) were packaged and highly purified resulting in genomic titers up to 3 × 1011/mL. Cells obtained from 24 patients with B-CLL were infected with AAV/EGFP or AAV/CD40L at a multiplicity of infection (MOI) of 100 resulting in transgene expression in up to 97% of cells as detected by flow cytometry 48 hours after infection. Viral transduction could be specifically blocked by heparin. Transduction with AAV/CD40L resulted in up-regulation of the costimulatory molecule CD80 not only on infected CLL cells but also on noninfected bystander leukemia B cells, whereas this effect induced specific proliferation of HLA-matched allogeneic T cells. Vaccination strategies for patients with B-CLL using leukemia cells infected ex vivo by rAAV vectors now seems possible in the near future.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 100,
Pages: 1655-1661
Publisher
American Society of Hematology
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)
CCG Hematopoetic Cell Transplants (IMI-KHZ)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)
CCG Hematopoetic Cell Transplants (IMI-KHZ)