Oncolytic Viral Therapy for Neuroendocrine Cancers
Researcher: Charles Rudin, MD, PhD Location: Johns Hopkins University - Sidney Kimmel Comprehensive Cancer Center State: Maryland Year: 2011 Status: Finished
This grant was issued in partnership with American Association for Cancer Research
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To define components of the Seneca Valley Virus (SVV-001) viral entry pathway, and to explore determinants of productive cytolytic infection with SVV-001.
Dr. Rudin is one of the recipients of the 2011 Caring for Carcinoid Foundation-AACR Grants for Carcinoid Tumor and Neuroendocrine Tumor Research. CFCF is pleased to announce the first cohort of winners of this award issued in partnership with the American Association for Cancer Research to: advance the understanding of neuroendocrine tumors; elucidate the mechanisms of currently available therapies; and identify new treatment targets for neuroendocrine tumors.
“By studying the Seneca Valley Virus, we hope to define a novel, targeted therapeutic strategy for patients with neuroendocrine cancers, in particular more aggressive neuroendocrine cancers such as atypical carcinoid.” – Dr. Charles Rudin
Dr. Rudin’s laboratory focuses on the development of novel cancer therapeutics including the Seneca Valley Virus, a small RNA virus that can selectively infect and destroy certain cancers, especially cancers with neuroendocrine features. Dr. Rudin developed and directed the first in-human phase 1 clinical trial of the Seneca Valley Virus (SVV-001). Neotropix, a biotechnology company based in Malvern PA, is currently developing SVV-001 commercially under the trade name NTX-010.
This innovative project will study the only anti-cancer virus with selective affinity for neuroendocrine tumor cells and define the population of neuroendocrine patients most likely to respond to SVV-001.
Specifically, Dr. Rudin and his team propose to elucidate the determinants of Seneca Valley Virus permissivity into neuroendocrine tumor cells. This information will enable molecular profiling of patient’s tumors to focus future clinical development on the patient population most likely to benefit.
This research is both exciting and innovative:
It represents a novel, targeted treatment strategy for neuroendocrine cancer patients;
It offers a personalized medicine approach to guide future clinical development;
Patients with the most aggressive neuroendocrine cancers may benefit most!
To define components of the SVV-001 viral entry pathway;
To explore determinants of productive cytolytic infection with SVV-001;
To allow future clinical trials of SVV-001 to target the patient population most likely to benefit from this approach.
My research group has focused on the development of novel cancer therapeutics, both in the laboratory and in the clinic. We have a particular interest in small cell lung cancer and other aggressive neuroendocrine cancers, including atypical carcinoid. Standard approaches to aggressive neuroendocrine cancers have changed minimally over the past 20 years. Novel therapeutic concepts are critically needed for these relatively rare but deadly cancers. My laboratory has been characterizing a novel picornavirus, SVV-001, which can selectively infect and destroy cancers with neuroendocrine differentiation. SVV-001 demonstrates a broad spectrum of activity against neuroendocrine tumors: about 50% of small cell carcinoma lines are permissive for the virus, as are a variety of other aggressive neuroendocrine cancers. The molecular and cellular determinants of SVV-001 permissivity have not been defined. We are seeking to identify the mechanisms of SVV-001 tumor cell entry as well as other cellular determinants of susceptibility to viral infection and lysis, using both innovative approaches and strategies that have been successfully used in defining the biology of other picornaviruses such as poliovirus. With the generous support of the Caring for Carcinoid Foundation and the American Association for Cancer Research, we will conduct a series of studies to define the basis of the selective tropism of SVV-001 for neuroendocrine tumors. These studies may identify biomarkers of viral permissivity, which will help guide subsequent clinical application of SVV-001 in patients with advanced neuroendocrine tumors. It is a terrific honor to receive this award in support of our work.
Research Progress and Results:
Identified a way to select patients most likely to respond to therapy using the Seneca Valley Virus (SVV-001), a known anti-cancer virus.
Dr. Rudin’s project sought to define the characteristics of neuroendocrine cancers that might be successfully treated with an anti-cancer virus called SVV-001. He focused mostly on neuroendocrine cancers of the lung, in particular the most deadly type, small cell lung cancer. Approximately 40% of small cell lung cancers are sensitive to this viral therapy. Dr. Rudin found a single pair of key genes (called ASCL1 and NEUROD1) whose relative levels are an easy and clinically applicable predictor of sensitivity to this treatment. These findings have clear implications for future clinical trials of SVV-001, suggesting a clear selection strategy to identify patients most likely to benefit from this novel therapeutic approach.