Suicide-gene-transduced T-cells for the regulation of the graft-versus-leukemia effect.
In allogeneic marrow transplantation (BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia and immune reconstitution. However, their use is limited by the risk of severe graft-vs-host disease (GvHD). Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. In the first pilot study, infusions of donor lymphocytes transduced with the Herpes Simplex virus thymidine kinase (HSV-tk) suicide resulted in anti-tumor activity in 50% of patients. Acute GvHD could be effectively controlled by ganciclovir-induced elimination of the transduced cells. If these results will be confirmed in larger studies, genetic manipulation of donor lymphocytes will increase efficacy and safety of allogeneic marrow transplantation.
Bonini
C
C
Telethon Institute for Gene Therapy (TIGET), Milano, Italy.
Ciceri
F
F
Marktel
S
S
Bordignon
C
C
D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016923:Cell Death; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D019868:Kanamycin Kinase / Q000235:genetics; D011355:Prodrugs / Q000493:pharmacokinetics*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012449:Safety; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D011355:Prodrugs; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; C092309:ganciclovir triphosphate; D013937:Thymidine Kinase; D019868:Kanamycin Kinase; D015774:Ganciclovir