Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers.
BACKGROUND
Numerous clinical trials have demonstrated that oncolytic viruses can elicit antitumor responses when they are administered directly into localized cancers. However, the treatment of metastatic disease with oncolytic viruses has been challenging due to the inactivation of viruses by components of human blood and/or to inadequate tumor selectivity.


METHODS
We determined the cytolytic potential and selectivity of Seneca Valley Virus-001 (SVV-001), a newly discovered native picornavirus, in neuroendocrine and pediatric tumor cell lines and normal cells. Suitability of the virus for intravenous delivery in humans was assessed by blood inactivation assays. Safety was evaluated in vivo using an immune-competent mouse model, and efficacy was evaluated in vivo in athymic mice bearing tumors derived from human small-cell lung cancer and retinoblastoma cell lines.


RESULTS
Cell lines derived from small-cell lung cancers and solid pediatric cancers were at least 10,000-fold more sensitive to the cytolytic activity of SVV-001 than were any of the adult normal human cells tested. Viral infectivity was not inhibited by human blood components. Intravenous doses up to 1 x 10(14) virus particles (vp) per kg were well tolerated, and no dose-limiting toxicity was observed in immune-competent mice. A single intravenous dose of 1 x 10(8) vp per kg into athymic mice bearing preestablished small-cell lung or retinoblastoma tumors resulted in complete, durable responses in ten of ten and five of eight mice, respectively.


CONCLUSIONS
SVV-001 has potent cytolytic activity and high selectivity for tumor cell lines having neuroendocrine properties versus adult normal cells. Systemically administered SVV-001 has potential for the treatment of metastatic neuroendocrine cancers.
Reddy
P Seshidhar
PS
Neotropix, Inc, 351 Phoenixville Pike, Malvern, PA 19355, USA.
Burroughs
Kevin D
KD
Hales
Laura M
LM
Ganesh
Shanthi
S
Jones
Brian H
BH
Idamakanti
Neeraja
N
Hay
Carl
C
Li
Shawn S
SS
Skele
Kristine L
KL
Vasko
Ann-Jeanette
AJ
Yang
Jingping
J
Watkins
D Neil
DN
Rudin
Charles M
CM
Hallenbeck
Paul L
PL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy / Q000628:therapy*; D018288:Carcinoma, Small Cell / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006386:Hemagglutination Tests; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000145:classification / Q000472:pathogenicity; D010849:Picornaviridae / Q000145:classification / Q000472:pathogenicity; D012107:Research Design; D012175:Retinoblastoma / Q000628:therapy; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents