Rapid salvage treatment with virus-specific T cells for therapy-resistant disease.
BACKGROUND
Viral infections are major complications after allogeneic hematopoietic stem cell transplantation (HSCT). During posttransplant immunosuppression the regular T-cell control is compromised. Even if treatment strategies against infections caused by herpes viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus have improved, the mortality rate is still considerable. If primary antiviral therapy fails or cannot be tolerated, adoptive therapy with virus-specific cytotoxic T cells (CTL) can be utilized.


METHODS
In this study, we used virus-specific CTLs to treat 8 patients suffering from severe viral infections after allogeneic HSCT. Using positive selection with HLA multimers and magnetic beads, we isolated CTLs from both frozen donor material as well as third-party donors within hours.


RESULTS
At 90 days after CTL infusions 7 out of 8 patients were still living. CTLs infused from third-party donors were detected in 5 of 6 patients up to 76 days after infusion. No graft-versus-host disease associated with CTL infusions was observed.


CONCLUSIONS
Our separation approach offers a rapid alternative for adoptive CTL therapy if primary antiviral treatment strategies fail. Because no prolonged expansion steps are needed, this method may be used for early treatment of patients suffering from life-threatening infectious complications.
Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. Michael.uhlin@ki.se
Michael
M
Uhlin
Jens
J
Gertow
Mehmet
M
Uzunel
Mantas
M
Okas
Sofia
S
Berglund
Emma
E
Watz
Mats
M
Brune
Per
P
Ljungman
Mark
M
Maeurer
Jonas
J
Mattsson
D000293:Adolescent; D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D002675:Child, Preschool; D004266:DNA Virus Infections / Q000276:immunology / Q000628:therapy*; D004267:DNA Viruses / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005190:Family; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease; D006680:HLA Antigens / Q000097:blood / Q000145:classification; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens