Application of pseudotyped lentivirus-mediated double suicide genes to allogeneic bone marrow transplantation in mice / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 82-86, 2004.
Article
in Chinese
| WPRIM
| ID: wpr-291470
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Administration of CD + TK gene-modified donor T cells to recipient in allo-BMT might be an approach to mitigate GVHD without compromising alloengraftment.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Therapeutics
/
Thymidine Kinase
/
Transplantation, Homologous
/
Body Weight
/
Genetic Therapy
/
Bone Marrow Transplantation
/
Lentivirus
/
Cytosine Deaminase
/
Genetics
Limits:
Animals
Language:
Chinese
Journal:
Chinese Journal of Hematology
Year:
2004
Type:
Article
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