Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program.
BACKGROUND
Seneca Valley virus (NTX-010) is a non-recombinant, replication competent RNA virus that is undergoing phase 1 clinical trials in adults for tumors with neuroendocrine characteristics. Here we have evaluated the antitumor activity of NTX-010 administered systemically.


METHODS
In vitro NTX-010 was tested against 23 cell lines exposed for 96 hr at 1 x 10(-4) to 10(4) viral particles (vp)/cell. In vivo NTX-010 was administered intravenously once at 3 x 10(12) vp/kg. Three measures of antitumor activity were used: (1) an objective response measure modeled after the clinical setting; (2) a treated to control (T/C) tumor volume measure; and (3) a time to event (fourfold increase in tumor volume for solid tumor models), measure based on the median event-free survival (EFS) of treated and control animals for each xenograft.


RESULTS
In vitro NTX-010 demonstrated a marked cytotoxic effect in a subset of the cell lines from the neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma panels. In vivo the most consistent activity was observed for the rhabdomyosarcoma and the neuroblastoma panels, with all four of the alveolar rhabdomyosarcoma xenografts and four of five neuroblastoma xenografts achieving CR or maintained CR. Objective responses were also observed in the rhabdoid tumor, Wilms tumor, and glioblastoma panels.


CONCLUSIONS
NTX-010 demonstrated a high level of activity both in vitro and in vivo. Further analysis of existing testing and molecular characterization data may help define the biological characteristics of cancer cells that are associated with response to NTX-010.
Morton
Christopher L
CL
St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Houghton
Peter J
PJ
Kolb
E Anders
EA
Gorlick
Richard
R
Reynolds
C Patrick
CP
Kang
Min H
MH
Maris
John M
JM
Keir
Stephen T
ST
Wu
Jianrong
J
Smith
Malcolm A
MA
D000818:Animals; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy; D050130:Oncolytic Virotherapy / Q000379:methods*; D012328:RNA Viruses; D012208:Rhabdomyosarcoma / Q000473:pathology / Q000628:therapy; D012512:Sarcoma, Ewing / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays