Treatment of intracerebral neoplasia and neoplastic meningitis with regional delivery of oncolytic recombinant poliovirus.
OBJECTIVE
Spread to the central nervous system (CNS) and the leptomeninges is a frequent complication of systemic cancers that is associated with serious morbidity and high mortality. We have evaluated a novel therapeutic approach against CNS complications of breast cancer based on the human neuropathogen poliovirus (PV).


METHODS
Susceptibility to PV infection and ensuing rapid cell lysis is mediated by the cellular receptor of PV, CD155. We evaluated CD155 expression in several human breast tumor tissue specimens and cultured breast cancer cell lines. In addition, we tested an oncolytic PV recombinant for efficacy in xenotransplantation models of neoplastic meningitis and cerebral metastasis secondary to breast cancer.


RESULTS
We observed that breast cancer tissues and cell lines derived thereof express CD155 at levels mediating exquisite sensitivity toward PV-induced oncolysis in the latter. An association with the immunoglobulin superfamily molecule CD155 renders breast cancer a likely target for oncolytic PV recombinants. This assumption was confirmed in xenotransplantation models for neoplastic meningitis or solitary cerebral metastasis, where local virus treatment dramatically improved survival.


CONCLUSIONS
Our findings suggest oncolytic PV recombinants as a viable treatment option for CNS complications of breast cancer.
Ochiai
Hidenobu
H
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Moore
Stephanie A
SA
Archer
Gary E
GE
Okamura
Tatsunori
T
Chewning
Tracy A
TA
Marks
Jeffrey R
JR
Sampson
John H
JH
Gromeier
Matthias
M
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D008577:Meningeal Neoplasms / Q000628:therapy*; D017955:Poliovirus / Q000235:genetics* / Q000254:growth & development; D051381:Rats; D011923:Rats, Nude; D011991:Receptors, Virus / Q000096:biosynthesis; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
D004274:DNA, Recombinant; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor