Phase I trial of Seneca Valley Virus (NTX-010), a newly discovered systemically deliverable oncolytic picornavirus, in patients with solid tumors with neuroendocrine features
| العنوان: | Phase I trial of Seneca Valley Virus (NTX-010), a newly discovered systemically deliverable oncolytic picornavirus, in patients with solid tumors with neuroendocrine features |
|---|---|
| المؤلفون: | J. R. Neefe, P. L. Hallenbeck, P. S. Reddy, L. M. Hales, D. Lansey, Charles M. Rudin, Kevin D. Burroughs |
| المصدر: | Journal of Clinical Oncology. 25:18014-18014 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Cancer Research, Picornavirus, biology, business.industry, biology.organism_classification, Selective cytotoxicity, Seneca Valley virus, Virology, Oncolytic virus, Cytolysis, Oncology, Medicine, In patient, business, Tropism |
| الوصف: | 18014 Background: NTX-010 is a replication-competent cytolytic picornavirus with selective tropism for cancers with neuroendocrine features. NTX-010 mediates high selective cytotoxicity for tumor cells with neuroendocrine properties and has no cytotoxicity on any human adult cell type tested. Antitumor efficacy has been demonstrated in 11/11 xenograft models, including metastatic, orthotopic, and syngeneic models. Intravenous (IV) administration of doses as low as 107 vp/kg are effective in xenograft models of small cell lung cancer. No significant toxicity in animals is seen at doses up to 1013 vp/kg. Methods: We initiated a single dose administration phase I dose-escalation study in patients with advanced solid tumors with neuroendocrine markers (CD56+, synaptophysin+, or chromogranin A+), starting at 107 vp/kg IV over 1h. Planned dose escalation is in log increments. Results: The first dose cohort has been completed, with no dose-limiting toxicities observed. Low grade fever, chills, arthralgias and myalgias starting 3 - 4 days after virus administration and lasting less than a week have been noted. The first study subject, with a widely metastatic small cell cancer with bladder invasion, demonstrated viral replication in vivo peaking d4 with >10,000-fold amplification of the input dose. This subject had complete clearance of infectious virus by day 17, but persistence of viral RNA detectable by RT-PCR in blood and urine until the time of her death from metastatic cancer on day 28. Autopsy demonstrated extensive intratumoral necrosis, and immunohistochemistry confirmed the presence of NTX-010 capsid protein in liver metastases but not adjacent normal liver. Conclusions: NTX-010 is a novel first-in-class anticancer virus with selective tropism for tumors with neuroendocrine features. This is the first anticancer virus given intravenously with documented selective intratumoral infection and replication. Administration was well tolerated. Safety data and viral kinetics will be presented. No significant financial relationships to disclose. |
| تدمد: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2007.25.18_suppl.18014 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::936c55ff103a7a4363977d3210be41bd https://doi.org/10.1200/jco.2007.25.18_suppl.18014 |
| رقم الانضمام: | edsair.doi...........936c55ff103a7a4363977d3210be41bd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
|---|---|
| DOI: | 10.1200/jco.2007.25.18_suppl.18014 |