In vitro thymidine kinase/ganciclovir-based suicide gene therapy using replication defective herpes simplex virus-1 against leukemic B-cell malignancies (MCL, HCL, B-CLL).
A replication defective herpes simplex virus-1 was evaluated as a therapeutic vector. Mantle cell lymphoma (MCL), hairy cell leukemia (HCL), and B-cell chronic lymphocytic leukemia (B-CLL) were chosen because leukemic cells were collectable from peripheral bloods in these diseases. Cells from six MCL, one HCL, and nine B-CLL were infected in vitro with T0Z.1 at 3 multiplicity of infection (MOI). Herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV)-mediated suicide gene therapy showed 14.7% of mean tumor killing against leukemic B-cell malignancies. The mean tumor-killing effects were 8.7 and 17.1% in MCL and B-CLL, respectively. The effect against HCL was 29%. The study indicates that herpes simplex virus (HSV)-based gene therapy might be an effective strategy.
Misumi
Motohiro
M
First Department of Internal Medicine, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. misumoto@saitama-med.ac.jp
Suzuki
Toshiya
T
Moriuchi
Shusuke
S
Glorioso
Joseph C
JC
Bessho
Masami
M
D000328:Adult; D000368:Aged; D002470:Cell Survival; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000633:toxicity; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D015448:Leukemia, B-Cell / Q000473:pathology / Q000628:therapy*; D007943:Leukemia, Hairy Cell / Q000473:pathology / Q000628:therapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology / Q000628:therapy; D020522:Lymphoma, Mantle-Cell / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic
D013937:Thymidine Kinase; D015774:Ganciclovir