First-in-man clinical results with good manufacturing practice (GMP)-compliant polypeptide-expanded adenovirus-specific T cells after haploidentical hematopoietic stem cell transplantation.
Adoptive immunotherapy against viral infections is a promising treatment option for patients after hematopoietic stem cell transplantation. However, the generation of virus-specific T cells is either cost-intensive or time-consuming. We developed the first GMP-compliant protocol to generate donor-derived adenovirus (HAdV), cytomegalovirus, and Epstein-Barr virus-specific T-cell lines (TCLs) within 12 days by the use of overlapping polypeptides derived from different viruses in combination with IL-15. Two patients after undergoing haploidentical hematopoietic stem cell transplantation with HAdV viremia displaying rising viral loads despite treatment with cidofovir received 1×10 donor-derived short-term expanded HAdV-specific TCLs per kg body weight. In both patients, HAdV-specific T cells could be detected by IFN-γ-ELISpot 30 and 22 days postinfusion, and resulted in complete clearance or >1.5 log reduction of viral load within 15 and 18 days, respectively. This protocol facilitates rapid and cost-effective generation of virus-specific TCLs, which appear to provide an effective treatment option.
Departments of *Clinical Cell Biology and FACS Core Unit †Quality Management ∥Molecular Microbiology, Children´s Cancer Research Institute (CCRI) ‡St. Anna Children´s Hospital #Department of Stem Cell Transplantation, St. Anna Children´s Hospital Departments of §Pediatrics ¶Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria **Institute of Pathology, Charité Unversitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
René
R
Geyeregger
Christine
C
Freimüller
Julia
J
Stemberger
Michaela
M
Artwohl
Volker
V
Witt
Thomas
T
Lion
Gottfried
G
Fischer
Anita
A
Lawitschka
Julia
J
Ritter
Michael
M
Hummel
Wolfgang
W
Holter
Gerhard
G
Fritsch
Susanne
S
Matthes-Martin
D000258:Adenovirus Infections, Human / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D000260:Adenoviruses, Human / Q000145:classification / Q000276:immunology*; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods / Q000592:standards; D007223:Infant; D008297:Male; D010455:Peptides / Q000494:pharmacology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D019562:Viral Load
D010455:Peptides