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Next Generation Animal Models to Deinfe Therapies for NETS

Pawel Mazur, PhD

Year: 2018
Institution: University of Texas M.D. Anderson Cancer Center
Country: United States
State: TX
Award Type: Collaborative
NET Type: Pancreas
Science Type: Basic

General Description

This innovative project will study an 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.

Results

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.

Publications

Miles LA, Burga LN, Gardner EE, Bostina M, Poirier JT, Rudin CM. Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. J Clin Invest. 2017 Aug 1; 127(8): 2957–2967. Published online 2017 Jun 26. doi: 10.1172/JCI93472

Citations

1: Cao L, Zhang R, Liu T, Sun Z, Hu M, Sun Y, Cheng L, Guo Y, Fu S, Hu J, Li X, Yu C, Wang H, Chen H, Li X, Fry EE, Stuart DI, Qian P, Lou Z, Rao Z. Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1. Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13087-13092. doi: 10.1073/pnas.1814309115. Epub 2018 Dec 4. PubMed PMID: 30514821; PubMed Central PMCID: PMC6304951.

2: Evans DJ, Wasinger AM, Brey RN, Dunleavey JM, St Croix B, Bann JG. Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth. Front Oncol. 2018 Nov 6;8:506. doi: 10.3389/fonc.2018.00506. eCollection 2018. Review. PubMed PMID: 30460197; PubMed Central PMCID: PMC6232524.

3: Wang Z, Zhang X, Yan R, Yang P, Wu Y, Yang D, Bian C, Zhao J. Emergence of a novel recombinant Seneca Valley virus in Central China, 2018. Emerg Microbes Infect. 2018 Nov 14;7(1):180. doi: 10.1038/s41426-018-0183-1. PubMed PMID: 30425243; PubMed Central PMCID: PMC6234214.

4: Jayawardena N, Burga LN, Easingwood RA, Takizawa Y, Wolf M, Bostina M. Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus. Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10934-E10940. doi: 10.1073/pnas.1810664115. Epub 2018 Oct 31. PubMed PMID: 30381454; PubMed Central PMCID: PMC6243253.

5: Yeung ML, Jia L, Yip CCY, Chan JFW, Teng JLL, Chan KH, Cai JP, Zhang C, Zhang AJ, Wong WM, Kok KH, Lau SKP, Woo PCY, Lo JYC, Jin DY, Shih SR, Yuen KY. Human tryptophanyl-tRNA synthetase is an IFN-γ-inducible entry factor for Enterovirus. J Clin Invest. 2018 Nov 1;128(11):5163-5177. doi: 10.1172/JCI99411. Epub 2018 Oct 15. PubMed PMID: 30153112; PubMed Central PMCID: PMC6205371.

6: Zhang X, Zhu Z, Yang F, Cao W, Tian H, Zhang K, Zheng H, Liu X. Review of Seneca Valley Virus: A Call for Increased Surveillance and Research. Front Microbiol. 2018 May 11;9:940. doi: 10.3389/fmicb.2018.00940. eCollection 2018. Review. PubMed PMID: 29867849; PubMed Central PMCID: PMC5958643.

7: Strauss M, Jayawardena N, Sun E, Easingwood R, Burga LN, Bostina M. Cryo-EM Structure of Seneca Valley Virus Procapsid. J Virol. 2017 Dec 20. pii: JVI.01927-17. doi: 10.1128/JVI.01927-17. [Epub ahead of print] PubMed PMID: 29263256; PubMed Central PMCID: PMC5827394.

Rudin CM, Poirier JT, Senzer NN, Stephenson J Jr, Loesch D, Burroughs KD, Reddy PS, Hann CL, Hallenbeck PL. Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features. Clin Cancer Res. 2011 Feb 15;17(4):888-95. doi: 10.1158/1078-0432.CCR-10-1706. Epub 2011 Feb 8.

Citations

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2: Evans DJ, Wasinger AM, Brey RN, Dunleavey JM, St Croix B, Bann JG. Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth. Front Oncol. 2018 Nov 6;8:506. doi: 10.3389/fonc.2018.00506. eCollection 2018. Review. PubMed PMID: 30460197; PubMed Central PMCID: PMC6232524.

3: Jayawardena N, Burga LN, Easingwood RA, Takizawa Y, Wolf M, Bostina M. Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus. Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10934-E10940. doi: 10.1073/pnas.1810664115. Epub 2018 Oct 31. PubMed PMID: 30381454; PubMed Central PMCID: PMC6243253.

4: Zhang X, Zhu Z, Yang F, Cao W, Tian H, Zhang K, Zheng H, Liu X. Review of Seneca Valley Virus: A Call for Increased Surveillance and Research. Front Microbiol. 2018 May 11;9:940. doi: 10.3389/fmicb.2018.00940. eCollection 2018. Review. PubMed PMID: 29867849; PubMed Central PMCID: PMC5958643.

5: Strauss M, Jayawardena N, Sun E, Easingwood R, Burga LN, Bostina M. Cryo-EM Structure of Seneca Valley Virus Procapsid. J Virol. 2017 Dec 20. pii: JVI.01927-17. doi: 10.1128/JVI.01927-17. [Epub ahead of print] PubMed PMID: 29263256; PubMed Central PMCID: PMC5827394.

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7: Jhawar SR, Thandoni A, Bommareddy PK, Hassan S, Kohlhapp FJ, Goyal S, Schenkel JM, Silk AW, Zloza A. Oncolytic Viruses-Natural and Genetically Engineered Cancer Immunotherapies. Front Oncol. 2017 Sep 11;7:202. doi: 10.3389/fonc.2017.00202. eCollection 2017. Review. PubMed PMID: 28955655; PubMed Central PMCID: PMC5600978.

8: Miles LA, Burga LN, Gardner EE, Bostina M, Poirier JT, Rudin CM. Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. J Clin Invest. 2017 Aug 1;127(8):2957-2967. doi: 10.1172/JCI93472. Epub 2017 Jun 26. PubMed PMID: 28650343; PubMed Central PMCID: PMC5531414.

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10: Qian S, Fan W, Liu T, Wu M, Zhang H, Cui X, Zhou Y, Hu J, Wei S, Chen H, Li X, Qian P. Seneca Valley Virus Suppresses Host Type I  Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage. J Virol. 2017 Jul 27;91(16). pii: e00823-17. doi: 10.1128/JVI.00823-17. Print 2017 Aug 15. PubMed PMID: 28566380; PubMed Central PMCID: PMC5533933.

11: Dvorak CM, Akkutay-Yoldar Z, Stone SR, Tousignant SJ, Vannucci FA, Murtaugh MP. An indirect enzyme-linked immunosorbent assay for the identification of antibodies to Senecavirus A in swine. BMC Vet Res. 2017 Feb 15;13(1):50. doi: 10.1186/s12917-017-0967-x. PubMed PMID: 28202026; PubMed Central PMCID: PMC5312445.

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21: Burke MJ, Ahern C, Weigel BJ, Poirier JT, Rudin CM, Chen Y, Cripe TP, Bernhardt MB, Blaney SM. Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: a report of the Children’s Oncology Group. Pediatr Blood Cancer. 2015 May;62(5):743-50. doi: 10.1002/pbc.25269. Epub 2014 Oct 12. PubMed PMID: 25307519; PubMed Central PMCID: PM4376652.

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