Co-expression of bfl-1 enhances host response in the herpes simplex virus-thymidine kinase/ganciclovir gene therapy system.
Anticancer suicide gene therapy using herpes simplex virus-thymidine kinase (HSV-tk) and ganciclovir (GCV) features the unique advantage of being able to elicit brisk host immune response against tumors and the host response reportedly can be potentiated with the co-expression of other appropriate immune- or apoptosis-related genes. We introduced a novel antiapoptotic gene, bfl-1, to test its applicability in the HSV-tk/GCV system. CT-26 murine colon cancer cells transfected with HSV-tk, alone or in combination with bcl-xL or bfl-1, were either grown in vitro or injected into syngeneic mice, followed by GCV administration. The co-expression of bfl-1 was associated with the upregulation of CD95 and CD40 ligand (CD40L) in vitro and with pronounced intratumoral T-lymphocyte infiltration in vivo. These results add to the previous findings that antiapoptotic genes can be used as an adjunctive component in the HSV-tk/GCV system to enhance host immune response against tumors.
Kwon
Ghee Young
GY
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwan-Dong, Kangnam Ku, 135-710, Seoul, Republic of Korea
Jeong
Jaehoon
J
Woo
Jong Kyu
JK
Choi
Hye Young
HY
Lee
Min-Jung
MJ
Ko
Jae-Kyun
JK
Shim
Yhong-Hee
YH
Kim
Chul-Woo
CW
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D023201:CD40 Ligand / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D010957:Plasmids / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D023201:CD40 Ligand; D013937:Thymidine Kinase; D015774:Ganciclovir