Use of a "replication-restricted" herpes virus to treat experimental human malignant mesothelioma.
Modified, nonneurovirulent herpes simplex viruses (HSVs) have shown promise in the treatment of brain tumors. However, HSV-1 can infect and lyse a wide range of cell types. In this report, we show that HSV-1716, a mutant lacking both copies of the gene coding ICP-34.5, can effectively treat a localized i.p. malignancy. Human malignant mesothelioma cells supported the growth of HSV-1716 and were efficiently lysed in vitro. i.p. injection of HSV-1716 into animals with established tumor nodules reduced tumor burden and significantly prolonged survival in an animal model of non-central nervous system-localized human malignancy without dissemination or persistence after i.p. injection into SCID mice bearing human tumors. These findings suggest that this virus may be efficacious and safe for use in localized human malignancies of nonneuronal origin such as malignant mesothelioma.
Kucharczuk
J C
JC
Thoracic Oncology Research Laboratory, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Randazzo
B
B
Chang
M Y
MY
Amin
K M
KM
Elshami
A A
AA
Sterman
D H
DH
Rizk
N P
NP
Molnar-Kimber
K L
KL
Brown
S M
SM
MacLean
A R
AR
Litzky
L A
LA
Fraser
N W
NW
Albelda
S M
SM
Kaiser
L R
LR
D000818:Animals; D015316:Genetic Therapy; D006801:Humans; D008654:Mesothelioma / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D018139:Simplexvirus / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication
D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1