[Application of pseudotyped lentivirus-mediated double suicide genes to allogeneic bone marrow transplantation in mice].
OBJECTIVE
To explore the feasibility and efficiency of cytosine deaminase (CD)/thymidine kinase (TK) gene-modified donor T cells used in allogeneic bone marrow transplantation (allo-BMT) as an approach to mitigate GVHD without compromising engraftment.


METHODS
The pseudotyped lentivirus vectors containing CD and TK double suicide genes were transfected with lipofectine to donor T cells. Lethally irradiated 615 leukemia mice were transplanted with BALB/c bone marrow plus CD(+)TK(+)T cells. GVHD prophylaxis was by administration of ganciclovir (GCV) and 5-Fluoride cytosine (5-FC).


RESULTS
The pseudotyped lentivirus-mediated gene transfer system could efficiently transfer CD and TK double suicide genes into donor T cells. Administration of GCV and 5-FC to the mice could markedly potentiate the CFU-S and CFU-GM yields and raise the number of peripheral white blood cells. 1 x 10(7) CD(+)TK(+) allogeneic T cells caused GVHD of a similar magnitude and time course to that of fresh, naive T cells after allo-BMT. Administration of GCV and 5-FC in mice received CD(+)TK(+)T cells reduced the severity of GVHD and resulted in significantly longer survival as compared with non-administration mice, and the effect was stronger than that of administration of GCV or 5-FC alone.


CONCLUSIONS
Administration of CD + TK gene-modified donor T cells to recipient in allo-BMT might be an approach to mitigate GVHD without compromising alloengraftment.
Jiang
Yi-rong
YR
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Chen
Xue-liang
XL
Ma
Dao-xin
DX
Liu
Chun-sheng
CS
D000818:Animals; D001835:Body Weight; D016026:Bone Marrow Transplantation; D043525:Cytosine Deaminase / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000473:pathology / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D013937:Thymidine Kinase / Q000235:genetics*; D014184:Transplantation, Homologous
D013937:Thymidine Kinase; D043525:Cytosine Deaminase