Distinct host cell fates for human malignant melanoma targeted by oncolytic rodent parvoviruses.
The rodent parvoviruses are known to be oncoselective, and lytically infect many transformed human cells. Because current therapeutic regimens for metastatic melanoma have low response rates and have little effect on improving survival, this disease is a prime candidate for novel approaches to therapy, including oncolytic parvoviruses. Screening of low-passage, patient-derived melanoma cell lines for multiplicity-dependent killing by a panel of five rodent parvoviruses identified LuIII as the most melanoma-lytic. This property was mapped to the LuIII capsid gene, and an efficiently melanoma tropic chimeric virus shown to undergo three types of interaction with primary human melanoma cells: (1) complete lysis of cultures infected at very low multiplicities; (2) acute killing resulting from viral protein synthesis and DNA replication, without concomitant expansion of the infection, due to failure to export progeny virions efficiently; or (3) complete resistance that operates at an intracellular step following virion uptake, but preceding viral transcription.
Medical Scientist Training Program, Yale University Medical School, 333 Cedar Street, New Haven, CT 06510, United States; Department of Genetics, Yale University Medical School, 333 Cedar Street, New Haven, CT 06510, United States.
Ellen M
EM
Vollmers
Peter
P
Tattersall
D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D008545:Melanoma / Q000821:virology*; D050504:Oncolytic Viruses / Q000254:growth & development*; D017992:Parvovirus / Q000254:growth & development*
Melanoma; Oncolytic parvovirus; Virus-induced cell death