Transfer of Autologous Gene-modified T Cells in HIV-infected Patients with Advanced Immunodeficiency and Drug-resistant Virus.
Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. We tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry-inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during anti-retroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus.
Infectious Diseases Unit, University Medical Center Hamburg-, Eppendorf, Hamburg, Germany. Electronic address: v.lunzen@uke.uni-hamburg.de.
Jan van
JV
Lunzen
Infectious Diseases Unit, University Medical Center Hamburg-, Eppendorf, Hamburg, Germany; Present address: private, practice, Berlin, Germany.
Tobias
T
Glaunsinger
Infectious Diseases Unit, University Medical Center Hamburg-, Eppendorf, Hamburg, Germany.
Ingrid
I
Stahmer
Department of Immunology, Laboratory Center, Berlin, Berlin, Germany.
Volker von
VV
Baehr
Department of Pediatric Hematology and Oncology, Hannover Medical, School, Hannover, Germany.
Christopher
C
Baum
EUFETS AG, Idar-Oberstein, Germany.
Andrea
A
Schilz
EUFETS AG, Idar-Oberstein, Germany.
Klaus
K
Kuehlcke
EUFETS AG, Idar-Oberstein, Germany.
Sonja
S
Naundorf
EUFETS AG, Idar-Oberstein, Germany; Georg-Speyer-Haus, Frankfurt a.M., Germany; Fresenius AG, Bad Homburg, Germany.
Holger
H
Martinius
Georg-Speyer-Haus, Frankfurt a.M., Germany.
Felix
F
Hermann
Georg-Speyer-Haus, Frankfurt a.M., Germany.
Tsanan
T
Giroglou
Georg-Speyer-Haus, Frankfurt a.M., Germany.
Sebastian
S
Newrzela
Georg-Speyer-Haus, Frankfurt a.M., Germany.
Ingrid
I
Müller
Georg-Speyer-Haus, Frankfurt a.M., Germany.
Francis
F
Brauer
Georg-Speyer-Haus, Frankfurt a.M., Germany; GANYMED Pharmaceuticals, AG, Mainz, Germany.
Gunda
G
Brandenburg
Fresenius AG, Bad Homburg, Germany.
Alexander
A
Alexandrov
Georg-Speyer-Haus, Frankfurt a.M., Germany. Electronic address: laer@em.uni-frankfurt.de.
Dorothee
D
von Laer