Advertisement

Journal of Neuro-Oncology

, Volume 128, Issue 1, pp 175–182 | Cite as

Neuro-oncology biotech industry progress report

  • Shamik ChakrabortyEmail author
  • Imithri Bodhinayake
  • Amrit Chiluwal
  • David J. Langer
  • Rosamaria Ruggieri
  • Marc Symons
  • John A. Boockvar
Meeting Proceedings

Abstract

The Brain Tumor Biotech Center at the Feinstein Institute for Medical Research, in collaboration with Voices Against Brain Cancer hosted The Brain Tumor Biotech Summit at in New York City in June 2015. The focus was once again on fostering collaboration between neuro-oncologist, neurosurgeons, scientists, leaders from biotechnology and pharmaceutical industries, and members of the financial community. The summit highlighted the recent advances in the treatment of brain tumor, and specifically focused on targeting of stem cells and EGFR, use of prophage and immunostimulatory vaccines, retroviral vectors for drug delivery, biologic prodrug, Cesium brachytherapy, and use of electric field to disrupt tumor cell proliferation. This article summarizes the current progress in brain tumor research as presented at 2015 The Brain Tumor Biotech Summit.

Keywords

Glioblastoma Brain tumors Biotechnology 

Notes

Compliance with ethical standards

Disclosures

The authors individually and as a whole have no relevant disclosures.

References

  1. 1.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, Groups EOfRaToCBTaR, Group NCIoCCT (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi: 10.1056/NEJMoa043330 CrossRefPubMedGoogle Scholar
  2. 2.
    Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740. doi: 10.1200/JCO.2008.19.8721 CrossRefPubMedGoogle Scholar
  3. 3.
    Institute NC (2015) National Cancer Institute Annual Plan and Budget Proposal—Fiscal Year 2016. National Cancer Institute. http://www.cancer.gov/about-nci/budget/annual-plan/nci-plan-2016.pdf. Accessed 1 Dec 2015
  4. 4.
    Ottenhausen M, Bodhinayake I, Banu M, Kesavabhotla K, Ray A, Boockvar JA (2013) Industry progress report on neuro-oncology: Biotech update 2013. J Neurooncol 115:311–316. doi: 10.1007/s11060-013-1222-3 CrossRefPubMedGoogle Scholar
  5. 5.
    Haber JS, Banu MA, Ray A, Kesavabhotla K, Boockvar JA (2013) Industry progress report on neuro-oncology: a biotech update. J Neurooncol 112:315–321. doi: 10.1007/s11060-012-1036-8 CrossRefPubMedGoogle Scholar
  6. 6.
    Boockvar J Brain Tumor Biotech Summit. Brain Tumor Biotech Summit, New York CityGoogle Scholar
  7. 7.
    Ashkenazi A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2:420–430. doi: 10.1038/nrc821 CrossRefPubMedGoogle Scholar
  8. 8.
    Abdulghani J, El-Deiry WS (2010) TRAIL receptor signaling and therapeutics. Expert Opin Ther Targets 14:1091–1108. doi: 10.1517/14728222.2010.519701 CrossRefPubMedGoogle Scholar
  9. 9.
    Wagner J, Kline CL, Pottorf RS, Nallaganchu BR, Olson GL, Dicker DT, Allen JE, El-Deiry WS (2014) The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity. Oncotarget 5:12728–12737CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Allen JE, Krigsfeld G, Patel L, Mayes PA, Dicker DT, Wu GS, El-Deiry WS (2015) Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer 14:99. doi: 10.1186/s12943-015-0346-9 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Prabhu VV, Allen JE, Dicker DT, El-Deiry WS (2015) Small-molecule ONC201/TIC10 targets chemotherapy-resistant colorectal cancer stem-like cells in an Akt/Foxo3a/TRAIL-dependent manner. Cancer Res 75:1423–1432. doi: 10.1158/0008-5472.CAN-13-3451 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Allen JE, Prabhu VV, Talekar M, van den Heuvel AP, Lim B, Dicker DT, Fritz JL, Beck A, El-Deiry WS (2015) Genetic and pharmacological screens converge in identifying FLIP, BCL2, and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anticancer agent ONC201/TIC10. Cancer Res 75:1668–1674. doi: 10.1158/0008-5472.CAN-14-2356 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Greer YE, Lipkowitz S (2015) TIC10/ONC201: a bend in the road to clinical development. Oncoscience 2:75–76CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Oncoceutics therapeutic approach. http://oncoceutics.com/therapeutic-approach/. Accessed 16 Nov 2015
  15. 15.
    Karpel-Massler G, Bâ M, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P, Siegelin MD (2015) TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo. Oncotarget. doi: 10.18632/oncotarget.5505 Google Scholar
  16. 16.
    Morre DJ, Morre DM (2012) ECTO-NOX proteins: growth, cancer, and aging. Springer Science, New York, pp 211–259CrossRefGoogle Scholar
  17. 17.
    Novogen (2015) TRXE-009 (Trilexium) moving towards a treatment for DIPG. http://www.novogen.com/pdf/trilexium.pdf. Accessed 16 Nov 2015
  18. 18.
    Bio A (2015) Prophage series vaccine. http://www.agenusbio.com/science/prophage.php. Accessed 16 Nov 2015
  19. 19.
    Eton O, Ross MI, East MJ, Mansfield PF, Papadopoulos N, Ellerhorst JA, Bedikian AY, Lee JE (2010) Autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96) in patients with metastatic melanoma. J Transl Med 8:9. doi: 10.1186/1479-5876-8-9 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, Gallino G, Piris A, Cattelan A, Lazzari I, Carrabba M, Scita G, Santantonio C, Pilla L, Tragni G, Lombardo C, Arienti F, Marchianò A, Queirolo P, Bertolini F, Cova A, Lamaj E, Ascani L, Camerini R, Corsi M, Cascinelli N, Lewis JJ, Srivastava P, Parmiani G (2002) Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol 20:4169–4180CrossRefPubMedGoogle Scholar
  21. 21.
    Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F, Isakov L, Flanigan R, Figlin R, Gupta R, Escudier B, Group C–RS (2008) An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 372:145–154. doi: 10.1016/S0140-6736(08)60697-2 CrossRefPubMedGoogle Scholar
  22. 22.
    Jonasch E, Wood C, Tamboli P, Pagliaro LC, Tu SM, Kim J, Srivastava P, Perez C, Isakov L, Tannir N (2008) Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings. Br J Cancer 98:1336–1341. doi: 10.1038/sj.bjc.6604266 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bloch O, Parsa AT (2014) Heat shock protein peptide complex-96 (HSPPC-96) vaccination for recurrent glioblastoma: a phase II, single arm trial. Neuro Oncol 16:758–759. doi: 10.1093/neuonc/nou054 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Boockvar J, Bodhinayake I, Brooks C, Chen J, Schwartz J, Rowinsky E, Reardon D (2014) Initiation of clinical studies with SL-701, a synthetic multi-peptide vaccine with enhanced immunostimulatory properties targeting multiple glioma-associated antigens, in adults with first recurrence of glioblastoma. Society for Neuro-Oncology Annual Scientific Meeting, 2014. Miami, Florida, USAGoogle Scholar
  25. 25.
    Padfield E, Ellis HP, Kurian KM (2015) Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma. Front Oncol 5:5. doi: 10.3389/fonc.2015.00005 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Guo G, Gong K, Wohlfeld B, Hatanpaa KJ, Zhao D, Habib AA (2015) Ligand-independent EGFR SIGNZALING. Cancer Res 75:3436–3441. doi: 10.1158/0008-5472.CAN-15-0989 CrossRefPubMedGoogle Scholar
  27. 27.
    Maire CL, Ligon KL (2014) Molecular pathologic diagnosis of epidermal growth factor receptor. Neuro Oncol 16(Suppl 8):viii1-6 doi: 10.1093/neuonc/nou294
  28. 28.
    CellDex (2015) Rindopepimut. http://www.celldex.com/pipeline/rindopepimut.php. Accessed 16 Nov 2015
  29. 29.
    Neagu MR, Reardon DA (2015) An update on the role of immunotherapy and vaccine strategies for primary brain tumors. Curr Treat Options Oncol 16:54. doi: 10.1007/s11864-015-0371-3 CrossRefPubMedGoogle Scholar
  30. 30.
    Schuster J, Lai RK, Recht LD, Reardon DA, Paleologos NA, Groves MD, Mrugala MM, Jensen R, Baehring JM, Sloan A, Archer GE, Bigner DD, Cruickshank S, Green JA, Keler T, Davis TA, Heimberger AB, Sampson JH (2015) A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro Oncol 17:854–861. doi: 10.1093/neuonc/nou348 CrossRefPubMedGoogle Scholar
  31. 31.
    Zussman BM, Engh JA (2015) Outcomes of the ACT III Study: Rindopepimut (CDX-110) therapy for glioblastoma. Neurosurgery 76:N17. doi: 10.1227/01.neu.0000465855.63458.0c CrossRefPubMedGoogle Scholar
  32. 32.
    Régina A, Demeule M, Ché C, Lavallée I, Poirier J, Gabathuler R, Béliveau R, Castaigne JP (2008) Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep-2. Br J Pharmacol 155:185–197. doi: 10.1038/bjp.2008.260 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Bertrand Y, Currie JC, Poirier J, Demeule M, Abulrob A, Fatehi D, Stanimirovic D, Sartelet H, Castaigne JP, Béliveau R (2011) Influence of glioma tumour microenvironment on the transport of ANG1005 via low-density lipoprotein receptor-related protein 1. Br J Cancer 105:1697–1707. doi: 10.1038/bjc.2011.427 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kurzrock R, Gabrail N, Chandhasin C, Moulder S, Smith C, Brenner A, Sankhala K, Mita A, Elian K, Bouchard D, Sarantopoulos J (2012) Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, and paclitaxel, in patients with advanced solid tumors. Mol Cancer Ther 11:308–316. doi: 10.1158/1535-7163.MCT-11-0566 CrossRefPubMedGoogle Scholar
  35. 35.
    Drappatz J, Brenner A, Wong ET, Eichler A, Schiff D, Groves MD, Mikkelsen T, Rosenfeld S, Sarantopoulos J, Meyers CA, Fielding RM, Elian K, Wang X, Lawrence B, Shing M, Kelsey S, Castaigne JP, Wen PY (2013) Phase I study of GRN1005 in recurrent malignant glioma. Clin Cancer Res 19:1567–1576. doi: 10.1158/1078-0432.CCR-12-2481 CrossRefPubMedGoogle Scholar
  36. 36.
    Angiochem (2015) Angiochem oncology. http://angiochem.com/oncology. Accessed 16 Nov 2015
  37. 37.
    Jiang H, Rugo HS (2015) Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options. Ther Adv Med Oncol 7:321–339. doi: 10.1177/1758834015599389 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Regina A, Demeule M, Tripathy S, Lord-Dufour S, Currie JC, Iddir M, Annabi B, Castaigne JP, Lachowicz JE (2015) ANG4043, a novel brain-penetrant peptide-mAb conjugate, is efficacious against HER2-positive intracranial tumors in mice. Mol Cancer Ther 14:129–140. doi: 10.1158/1535-7163.MCT-14-0399 CrossRefPubMedGoogle Scholar
  39. 39.
    Dalba C, Klatzmann D, Logg CR, Kasahara N (2005) Beyond oncolytic virotherapy: replication-competent retrovirus vectors for selective and stable transduction of tumors. Curr Gene Ther 5:655–667CrossRefPubMedGoogle Scholar
  40. 40.
    Nakamura H, Mullen JT, Chandrasekhar S, Pawlik TM, Yoon SS, Tanabe KK (2001) Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracil. Cancer Res 61:5447–5452PubMedGoogle Scholar
  41. 41.
    El-Tahtawy A, Wolf W (1991) In vivo measurements of intratumoral metabolism, modulation, and pharmacokinetics of 5-fluorouracil, using 19F nuclear magnetic resonance spectroscopy. Cancer Res 51:5806–5812PubMedGoogle Scholar
  42. 42.
    Huang TT, Hlavaty J, Ostertag D, Espinoza FL, Martin B, Petznek H, Rodriguez-Aguirre M, Ibañez CE, Kasahara N, Gunzburg W, Gruber HE, Pertschuk D, Jolly DJ, Robbins JM (2013) Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive glioblastoma model. Cancer Gene Ther 20:544–551. doi: 10.1038/cgt.2013.51 CrossRefPubMedGoogle Scholar
  43. 43.
    Twitty CG, Diago O, Hogan D, Burrascano C, Ibanez CE, Jolly D, Ostertag D (2015) Retroviral replicating vectors deliver cytosine deaminase leading to targeted 5-FU-mediated cytotoxicity in multiple human cancer types. Hum Gene Ther Methods. doi: 10.1089/hgtb.2015.106 PubMedGoogle Scholar
  44. 44.
    Tocagen (2015) TOCA 5: Phase 2/3 Trial for Recurrent GBM or AA. http://www.tocagen.com/toca5/. Accessed 16 Nov 2015
  45. 45.
    Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvão da Silva AP, Lin AH, Valenta DT, Perez OD, Ibañez CE, Chen CI, Pettersson PL, Burnett R, Daublebsky V, Hlavaty J, Gunzburg W, Kasahara N, Gruber HE, Jolly DJ, Robbins JM (2012) Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. Neuro Oncol 14:145–159. doi: 10.1093/neuonc/nor199 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Bradley KA, Mehta MP (2004) Management of brain metastases. Semin Oncol 31:693–701CrossRefPubMedGoogle Scholar
  47. 47.
    Tatter SB, Shaw EG, Rosenblum ML, Karvelis KC, Kleinberg L, Weingart J, Olson JJ, Crocker IR, Brem S, Pearlman JL, Fisher JD, Carson K, Grossman SA, Consortium NAtBTTCNS (2003) An inflatable balloon catheter and liquid 125I radiation source (GliaSite Radiation Therapy System) for treatment of recurrent malignant glioma: multicenter safety and feasibility trial. J Neurosurg 99:297–303. doi: 10.3171/jns.2003.99.2.0297 CrossRefPubMedGoogle Scholar
  48. 48.
    Wernicke AG, Yondorf MZ, Peng L, Trichter S, Nedialkova L, Sabbas A, Kulidzhanov F, Parashar B, Nori D, Clifford Chao KS, Christos P, Kovanlikaya I, Pannullo S, Boockvar JA, Stieg PE, Schwartz TH (2014) Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases. J Neurosurg 121:338–348. doi: 10.3171/2014.3.JNS131140 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Rogers LR, Rock JP, Sills AK, Vogelbaum MA, Suh JH, Ellis TL, Stieber VW, Asher AL, Fraser RW, Billingsley JS, Lewis P, Schellingerhout D, Shaw EG, Group BMS (2006) Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases. J Neurosurg 105:375–384. doi: 10.3171/jns.2006.105.3.375 CrossRefPubMedGoogle Scholar
  50. 50.
    Yang R, Wang J, Zhang H (2009) Dosimetric study of Cs-131, I-125, and Pd-103 seeds for permanent prostate brachytherapy. Cancer Biother Radiopharm 24:701–705. doi: 10.1089/cbr.2009.0648 CrossRefPubMedGoogle Scholar
  51. 51.
    Isoray (2015) Brain Cancer Treatment: the gold standard in brachytherapy for brain cancer. http://www.isoray.com/treatment/brain-cancer-treatment/. Accessed 16 Nov 2015
  52. 52.
    Novocure (2015) Use of tumor treatment fields for glioblastoma. http://www.novocure.com/our-therapy.aspx. Accessed 1 Dec 2015
  53. 53.
    Vymazal J, Wong ET (2014) Response patterns of recurrent glioblastomas treated with tumor-treating fields. Semin Oncol 41(Suppl 6):S14–S24. doi: 10.1053/j.seminoncol.2014.09.009 CrossRefPubMedGoogle Scholar
  54. 54.
    Stupp R, Taillibert S, Kanner A, Kesari S, Toms SA, Barnett GH, Fink KL, Silvani A, Lieberman FS, Zhu J-J, Taylor LP, Honnorat J, Hottinger A, Chen T, Tran DD, Kim C-y, Hirte HW, Hegi ME, Palti Y, Ram Z (2015) Tumor treating fields (TTFields): a novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma—First report of the full dataset of the EF14 randomized phase III trial. 2015 ASCO Annual Meeting. J Clin Oncol Chicago, IL, p suppl; abstr 2000Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Brain Tumor Biotech Center, Feinstein Institute for Medical ResearchHofstra Northwell School of MedicineManhassetUSA
  2. 2.Department of Neurological SurgeryHofstra Northwell School of MedicineManhassetUSA
  3. 3.Department of Neurological Surgery and Otolaryngology/Head and Neck Surgery, Lenox Hill Brain Tumor CenterLenox Hill HospitalNew YorkUSA

Personalised recommendations