HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.
In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus-induced lymphoma after T cell-depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.
Bonini
C
C
Telethon Institute for Gene Therapy (TIGET), Istituto Scientifico H. S. Raffaele, 20132 Milan, Italy.
Ferrari
G
G
Verzeletti
S
S
Servida
P
P
Zappone
E
E
Ruggieri
L
L
Ponzoni
M
M
Rossini
S
S
Mavilio
F
F
Traversari
C
C
Bordignon
C
C
D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000201:enzymology; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008232:Lymphoproliferative Disorders / Q000628:therapy; D010865:Pilot Projects; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014184:Transplantation, Homologous
D013937:Thymidine Kinase; D015774:Ganciclovir