SUMMARY OF INVENTION
MSK investigators have identified a clinically tractable predictive biomarker for permissivity of the Seneca Valley Virus (SVV), an oncolytic picornavirus that has demonstrated promise in neuroendocrine cancers.
SVV has been shown to selectively infect and lyse cancer cells with neuroendocrine features, notably small cell lung cancer (SCLC) and pediatric brain cancers. Phase 1 clinical trials testing SVV as a virotherapy in patients with neuroendocrine cancers showed high levels of sustained viral replication in SCLC patients, even after the production of neutralizing antibodies, and confirmed the ability of SVV to selectively infect cancer cells after IV administration. Prior clinical development of this agent has been hurt by a lack of understanding of the cellular determinants of infection, most notably the identification of the cellular receptor for SVV.
MSK researchers have identified the anthrax toxin receptor 1 (ANTXR1) protein as the receptor for SVV by utilizing two complementary genome-wide loss-of-function screens. This work definitively shows that ANTXR1 interacts directly and specifically with SVV, and that expression is required for SVV binding to permissive cells and subsequent infection.
This predictive biomarker could potentiate the promise of SVV oncotherapy in these patient populations, either as a single agent or in combination with additional immunotherapies.
Identifies patients most likely in specific indications to be responsive to SVV treatment
Simple diagnostic test focused on a single biomarker
Easily validated in tumor samples from past clinical trials
Small cell lung cancer is an extremely aggressive and almost universally lethal form of lung cancer, which accounts for approximately 15% of all lung cancer diagnoses annually and ~30,000 deaths in the U.S. Novel and more effective therapies are still desperately needed for SCLC, as the standard treatment has not improved in almost three decades.
Miles et al. (2017) Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. Journal of Clinical Investigation (link)
AREAS OF APPLICATION
Diagnostic, biomarker, viral oncotherapy
STAGE OF DEVELOPMENT
U.S. National application PCT/US2016/064679 published; Europe National application published; India National application pending
Charles R. Rudin, MD, PhD: Laboratory Head, Memorial Hospital Research Laboratories; Chief, Thoracic Oncology Service, Memorial Hospital; Co-Director, Druckenmiller Center for Lung Cancer Research; Sylvia Hassenfeld Chair in Lung Cancer Research
Lisa Kennedy, PhD