Project title: Oncolytic viral therapy for NETs

Charles Rudin, MD, PhD Johns Hopkins School of Medicine

Charles Rudin, MD, PhD
  • Status: Completed
  • Year(s): 2011
  • Research Type: Translational
  • Primary Site: Other
  • Area of Inquiry: Vaccine/virus

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

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.

1: Kaufman HL, Bommareddy PK. Two roads for oncolytic immunotherapy development. J Immunother Cancer. 2019 Feb 1;7(1):26. doi: 10.1186/s40425-019-0515-2. PubMed PMID: 30709365; PubMed Central PMCID: PMC6359832.

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.

6: Fountzilas C, Patel S, Mahalingam D. Review: Oncolytic virotherapy, updates and future directions. Oncotarget. 2017 May 31;8(60):102617-102639. doi: 10.18632/oncotarget.18309. eCollection 2017 Nov 24. Review. PubMed PMID: 29254276; PubMed Central PMCID: PMC5731986.

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.

9: Meyers DE, Wang AA, Thirukkumaran CM, Morris DG. Current Immunotherapeutic Strategies to Enhance Oncolytic Virotherapy. Front Oncol. 2017 Jun 6;7:114. doi: 10.3389/fonc.2017.00114. eCollection 2017. Review. PubMed PMID: 28634571; PubMed Central PMCID: PMC5459877.

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.

12: Ahmad Z, Kratzke RA. Novel oncolytic viral therapies in patients with thoracic malignancies. Oncolytic Virother. 2016 Dec 21;6:1-9. doi: 10.2147/OV.S116012. eCollection 2017. Review. PubMed PMID: 28053943; PubMed Central PMCID: PMC5189707.

13: Burke MJ. Oncolytic Seneca Valley Virus: past perspectives and future directions. Oncolytic Virother. 2016 Sep 6;5:81-9. doi: 10.2147/OV.S96915. eCollection 2016. Review. PubMed PMID: 27660749; PubMed Central PMCID: PMC5019429.

14: Downs-Canner S, Guo ZS, Ravindranathan R, Breitbach CJ, O’Malley ME, Jones HL, Moon A, McCart JA, Shuai Y, Zeh HJ, Bartlett DL. Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers. Mol Ther. 2016 Aug;24(8):1492-501. doi: 10.1038/mt.2016.101. Epub 2016 May 16. PubMed PMID: 27203445; PubMed Central PMCID: PMC5023393.

 

15: Ruiz AJ, Hadac EM, Nace RA, Russell SJ. MicroRNA-Detargeted Mengovirus for Oncolytic Virotherapy. J Virol. 2016 Mar 28;90(8):4078-4092. doi: 10.1128/JVI.02810-15. Print 2016 Apr. PubMed PMID: 26865716; PubMed Central PMCID: PMC4810567.

16: Geier B, Kurmashev D, Kurmasheva RT, Houghton PJ. Preclinical Childhood Sarcoma Models: Drug Efficacy Biomarker Identification and Validation. Front Oncol. 2015 Aug 26;5:193. doi: 10.3389/fonc.2015.00193. eCollection 2015. Review. PubMed PMID: 26380223; PubMed Central PMCID: PMC4549564.

17: Whitehurst M, Chiappori A. Immunotherapy treatments for small-cell lung cancer: past, present and future. Lung Cancer Manag. 2013;2(6):517-525. PubMed PMID: 26236401; PubMed Central PMCID: PMC4520540.

18: Miles LA, Brennen WN, Rudin CM, Poirier JT. Seneca Valley Virus 3Cpro Substrate Optimization Yields Efficient Substrates for Use in Peptide-Prodrug Therapy. PLoS One. 2015 Jun 12;10(6):e0129103. doi: 10.1371/journal.pone.0129103. eCollection 2015. Erratum in: PLoS One. 2015;10(8):e0136480. PubMed PMID: 26069962; PubMed Central PMCID: PMC4466507.

19: Buijs PR, Verhagen JH, van Eijck CH, van den Hoogen BG. Oncolytic viruses: From bench to bedside with a focus on safety. Hum Vaccin Immunother. 2015;11(7):1573-84. doi: 10.1080/21645515.2015.1037058. Review. PubMed PMID: 25996182; PubMed Central PMCID: PMC4514197.

20: Renner DN, Jin F, Litterman AJ, Balgeman AJ, Hanson LM, Gamez JD, Chae M, Carlson BL, Sarkaria JN, Parney IF, Ohlfest JR, Pirko I, Pavelko KD, Johnson AJ. Effective Treatment of Established GL261 Murine Gliomas through Picornavirus Vaccination-Enhanced Tumor Antigen-Specific CD8+ T Cell Responses. PLoS One. 2015 May 1;10(5):e0125565. doi: 10.1371/journal.pone.0125565. eCollection 2015. PubMed PMID: 25933216; PubMed Central PMCID: PMC4416934.

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.

22: Moehler M, Goepfert K, Heinrich B, Breitbach CJ, Delic M, Galle PR, Rommelaere J. Oncolytic virotherapy as emerging immunotherapeutic modality: potential of parvovirus h-1. Front Oncol. 2014 May 1;4:92. doi: 10.3389/fonc.2014.00092. eCollection 2014. Review. PubMed PMID: 24822170; PubMed Central PMCID: PMC4013456.

23: Miest TS, Cattaneo R. New viruses for cancer therapy: meeting clinical needs. Nat Rev Microbiol. 2014 Jan;12(1):23-34. doi: 10.1038/nrmicro3140. Epub 2013 Dec 2. Review. PubMed PMID: 24292552; PubMed Central PMCID: PMC4002503.

24: Poirier JT, Dobromilskaya I, Moriarty WF, Peacock CD, Hann CL, Rudin CM. Selective tropism of Seneca Valley virus for variant subtype small cell lung cancer. J Natl Cancer Inst. 2013 Jul 17;105(14):1059-65. doi: 10.1093/jnci/djt130. Epub 2013 Jun 5. PubMed PMID: 23739064; PubMed Central PMCID: PMC3888137.

25: Liu Z, Zhao X, Mao H, Baxter PA, Huang Y, Yu L, Wadhwa L, Su JM, Adesina A, Perlaky L, Hurwitz M, Idamakanti N, Police SR, Hallenbeck PL, Hurwitz RL, Lau CC, Chintagumpala M, Blaney SM, Li XN. Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor-based orthotopic xenograft mouse models of pediatric glioma. Neuro Oncol. 2013 Sep;15(9):1173-85. doi: 10.1093/neuonc/not065. Epub 2013 May 7. PubMed PMID: 23658322; PubMed Central PMCID: PMC3748915.

26: Pavelko KD, Bell MP, Karyampudi L, Hansen MJ, Allen KS, Knutson KL, Pease LR. The epitope integration site for vaccine antigens determines virus control while maintaining efficacy in an engineered cancer vaccine. Mol Ther. 2013 May;21(5):1087-95. doi: 10.1038/mt.2013.52. Epub 2013 Apr 9. PubMed PMID: 23568262; PubMed Central PMCID: PMC3666639.

27: Russell SJ, Peng KW, Bell JC. Oncolytic virotherapy. Nat Biotechnol. 2012 Jul 10;30(7):658-70. doi: 10.1038/nbt.2287. Review. PubMed PMID: 22781695; PubMed Central PMCID: PMC3888062.

28: Pietanza MC, Rudin CM. Novel therapeutic approaches for small cell lung cancer: the future has arrived. Curr Probl Cancer. 2012 May-Jun;36(3):156-73. doi: 10.1016/j.currproblcancer.2012.03.005. Epub 2012 Apr 10. PubMed PMID: 22495056; PubMed Central PMCID: PMC3392558.

29: Friedman GK, Cassady KA, Beierle EA, Markert JM, Gillespie GY. Targeting pediatric cancer stem cells with oncolytic virotherapy. Pediatr Res. 2012 Apr;71(4 Pt 2):500-10. doi: 10.1038/pr.2011.58. Epub 2012 Feb 15. Review. PubMed PMID: 22430386; PubMed Central PMCID: PMC3607376.

Additional Details

  • City: Baltimore
  • Grant Duration: 2 years
  • Grant Partner: American Association for Cancer Research (AACR)
  • Awards: No information
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