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Immunobiology and Immunotherapeutic Targeting of Glioma Stem Cells

  • Mecca Madany
  • Tom M. Thomas
  • Lincoln Edwards
  • John S. YuEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 853)

Abstract

For decades human brain tumors have confounded our efforts to effectively manage and treat patients. In adults, glioblastoma multiforme is the most common malignant brain tumor with a patient survival of just over 14 months. In children, brain tumors are the leading cause of solid tumor cancer death and gliomas account for one-fifth of all childhood cancers. Despite advances in conventional treatments such as surgical resection, radiotherapy, and systemic chemotherapy, the incidence and mortality rates for gliomas have essentially stayed the same. Furthermore, research efforts into novel therapeutics that initially appeared promising have yet to show a marked benefit. A shocking and somewhat disturbing view is that investigators and clinicians may have been targeting the wrong cells, resulting in the appearance of the removal or eradication of patient gliomas only to have brain cancer recurrence. Here we review research progress in immunotherapy as it pertains to glioma treatment and how it can and is being adapted to target glioma stem cells (GSCs) as a means of dealing with this potential paradigm.

Keywords

Glioma stem cells Glioblastoma Cancer stem cells Immunotherapy Cancer immunology 

References

  1. 1.
    Allegra A, Alonci A, Penna G, Innao V, Gerace D, Rotondo F, Musolino C. The cancer stem cell hypothesis: a guide to potential molecular targets. Cancer Invest. 2014;32(9):470–95. doi: 10.3109/07357907.2014.958231.PubMedCrossRefGoogle Scholar
  2. 2.
    Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumor initiating cells. Nature. 2004;432:396–401.PubMedCrossRefGoogle Scholar
  4. 4.
    Wang R, Chadalavada K, Wilshire J, et al. Glioblastoma-stem like cells give rise to tumor epithelium. Nature. 2010;468:829–35.PubMedCrossRefGoogle Scholar
  5. 5.
    Cheng L, Huang Z, Zhou W, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013;153(1):139–52.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Lathia JD, et al. High-throughput flow cytometry screening reveals a role for junctional adhesion molecule as a cancer stem cell maintenance factor. Cell Rep. 2014;6(1):117–29.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Bleau AM, Hambardzumyan D, Ozawa T, et al. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 2009;4(3):226–35.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Ignatova TN, Kukekov VG, Laywell ED, et al. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia. 2002;39:193–206.PubMedCrossRefGoogle Scholar
  9. 9.
    Xiangpeng Y, Curtin J, Xiong Y, et al. Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene. 2004;23:9392–400.CrossRefGoogle Scholar
  10. 10.
    Lee J, Kotliarova S, Kotliarov Y, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 2006;9:391–403.PubMedCrossRefGoogle Scholar
  11. 11.
    Wang J, Sakariassen PO, Tsinkalovsky O, et al. CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int J Cancer. 2008;122(4):761–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Joo KM, Kim SY, Song SY, et al. Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas. Lab Invest. 2008;88(4):808–15.PubMedCrossRefGoogle Scholar
  13. 13.
    Barcelos LS, Duplaa C, Krankel N, et al. Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling. Circ Res. 2009;104(9):1095–102.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Jin Son M, Woolard K, Nam D-H, et al. SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell. 2009;4(5):440–52.CrossRefGoogle Scholar
  15. 15.
    Anido J, Saez-Borderias A, Gonzalez-Junca A, et al. TGF-β receptor inhibitors target the CD44high/Id1high glioma-initiating cell population in human glioblastoma. Cancer Cell. 2010;18:655–68.PubMedCrossRefGoogle Scholar
  16. 16.
    Johnson LA, Sampson JH. Immunotherapy approaches for malignant glioma from 2007 to 2009. Curr Neurol Neurosci Rep. 2010;10(4):259–66.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    DeVita VT, Hellstrom S, Rosenberg SA. Biologic therapy of cancer, vol. 2. Philadelphia: J. B. Lippincott Company; 1995.Google Scholar
  18. 18.
    Butler TP, Grantham FH, Gullino PM. Bulk transfer of fluid in the interstitial compartment of mammary tumors. Cancer Res. 1975;35(11 Pt 1):3084–8. PubMed: 1182701.PubMedGoogle Scholar
  19. 19.
    Jain RK, Baxter LT. Mechanisms of heterogeneous distribution of monoclonal antibodies and other macro-molecules in tumors: significance of elevated interstitial pressure. Cancer Res. 1988;48(24 Pt 1):7022–32. PubMed: 3191477.PubMedGoogle Scholar
  20. 20.
    Williams LE, Duda RB, Proffitt RT, Beatty BG, Beatty JD, Wong JY, Shively JE, Paxton RJ. Tumor uptake as a function of tumor mass: a mathematic model. J Nucl Med. 1988;29(1):103–9.PubMedGoogle Scholar
  21. 21.
    Wikstrand CJ, Cokgor I, Sampson JH, et al. Monoclonal antibody therapy of human gliomas: current status and future approaches. Cancer Metastasis Rev. 1999;18(4):451–64.PubMedCrossRefGoogle Scholar
  22. 22.
    Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH. Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A. 1994;91(6):2076–80.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Cragg MS, French RR, Glennie MJ. Signaling antibodies in cancer therapy. Curr Opin Immunol. 1999;11(5):541–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Rivera F, Vega-Villegas ME, Lopez-Brea MF, Marquez R. Current situation of panitumumab, matuzumab, nimotuzumab and zalutumumab. Acta Oncol. 2008;47(1):9–19.PubMedCrossRefGoogle Scholar
  25. 25.
    Ohno M, Natsume A, Ichiro Iwami K, et al. Retrovirally engineered T-cell-based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen. Cancer Sci. 2010;101(12):2518–24.PubMedCrossRefGoogle Scholar
  26. 26.
    Eller JL, Longo SL, Hicklin DJ, et al. Activity of antiepidermal growth factor receptor monoclonal antibody C225 against glioblastoma multiforme. Neurosurgery. 2002;51(4):1005–14.PubMedGoogle Scholar
  27. 27.
    Faillot T, et al. A phase I study of an anti-epidermal growth factor receptor monoclonal antibody for the treatment of malignant gliomas. Neurosurgery. 1996;39:478–83.PubMedGoogle Scholar
  28. 28.
    Wikstrand CJ, McLendon RE, Friedman AH, Bigner DD. Cell surface localization and density of the tumor associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res. 1997;57(18):4130–40.PubMedGoogle Scholar
  29. 29.
    Zalutsky MR, Boskovitz A, Kuan CT, et al. Radioimmuno targeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors. Nucl Med Biol. 2012;39(1):23–34.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Yang W, Barth RF, Wu G, et al. Development of a syngeneic rat brain tumor model expressing EGFRvIII and its use for molecular targeting studies with monoclonal antibody L8A4. Clin Cancer Res. 2005;11(1):341–50.PubMedGoogle Scholar
  31. 31.
    Perera RM, Narita Y, Furnari FB, et al. Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity. Clin Cancer Res. 2005;11(17):6390–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Vredenburgh JJ, Desjardins A, Reardon DA, et al. The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma. Clin Cancer Res. 2011;17(12):4119–24.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene. 2000;19(56):6550–65.PubMedCrossRefGoogle Scholar
  34. 34.
    Gilbert MR, Dignam J, Won M, et al. RTOG 0825: phase III double-blind placebo-controlled trial evaluating Bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). J Clin Oncol. 2013;31(suppl;abstr 1).Google Scholar
  35. 35.
    Day ED, Lassiter S, Woodhall B, Mahaley JL, Mahaley MS. The localization of radioantibodies in human brain tumors. I. Preliminary exploration. Cancer Res. 1965;25(6):773–8.PubMedGoogle Scholar
  36. 36.
    Zalutsky MR. Targeted radiotherapy of brain tumours. Br J Cancer. 2004;90(8):1469–73.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD. Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res. 1983;43(6):2796–805.PubMedGoogle Scholar
  38. 38.
    Riva P, Arista A, Franceschi G, et al. Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors. Cancer Res. 1995;55(23 Suppl):5952s–6.PubMedGoogle Scholar
  39. 39.
    Rosenkranz AA, Vaidyanathan G, Pozzi OR, Lunin VG, Zalutsky MR, Sobolev AS. Engineered modular recombinant transporters: application of new platform for targeted radiotherapeutic agents to alpha-particle emitting 211 At. Int J Radiat Oncol Biol Phys. 2008;72(1):193–200.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    DeVita Jr VT, Lawrence TS, Rosenberg SA, et al., editors. Cancer: principles & practice of oncology. 9th ed. Philadelphia, PA: LWW; 2011.Google Scholar
  41. 41.
    Puri RK, Hoon DS, Leland P, Snoy P, Rand RW, Pastan I, Kreitman RJ. Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res. 1996;56(24):5631–7.PubMedGoogle Scholar
  42. 42.
    Sampson JH, Reardon DA, Friedman AH, Friedman HS, Coleman RE, McLendon RE, Pastan I, Bigner DD. Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study. Neuro Oncol. 2005;7(1):90–6.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    vom Berg J, Vrohlings M, Haller S, Haimovici A, Kulig P, Sledzinska A, Weller M, Becher B. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell mediated glioma rejection. J Exp Med. 2013;210:2803–11.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Hayes RL, Arbit E, Odaimi M, et al. Adoptive cellular immunotherapy for the treatment of malignant gliomas. Crit Rev Oncol Hematol. 2001;39(1–2):31–42.PubMedCrossRefGoogle Scholar
  45. 45.
    Grimm EA, Mazumder A, Zhang HZ, et al. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982;155(6):1823–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Rosenberg SA. The development of new immunotherapies for the treatment of cancer using interleukin-2. A review. Ann Surg. 1988;208:121–35.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1981;41(11 Pt 1):4420–5.PubMedGoogle Scholar
  48. 48.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA. In vitro killing of human glioblastoma by interleukin-2-activated autologous lymphocytes. J Neurosurg. 1986;64(1):114–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Ahmed N, Salsman VS, Kew Y, et al. HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors. Clin Cancer Res. 2010;16(2):474–85.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Kahlon KS, Brown C, Cooper LJ, Raubitschek A, Forman SJ, Jensen MC. Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res. 2004;64(24):9160–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Bullain SS, Sahin A, Szentirmai O, et al. Genetically engineered T cells to target EGFRvIII expressing glioblastoma. J Neurooncol. 2009;94(3):373–82.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med. 2013;5:215ra172.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Steinman RM, Cohn ZAJ. J Exp Med. 1973;137:1142–62.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Badhiwala J, Decker WK, Berens ME, Bhardwaj RD. Clinical trials in cellular immunotherapy for brain/CNS tumors. Expert Rev Neurother. 2013;13(4):405–24.PubMedCrossRefGoogle Scholar
  55. 55.
    Benencia F, Sprague L, McGinty J, Pate M, Muccioli M. Dendritic cells the tumor microenvironment and the challenges for an effective antitumor vaccination. J Biomed Biotechnol. 2012;2012:425–76.CrossRefGoogle Scholar
  56. 56.
    Ali-Osman F. Brain tumors. In: Masters JRW, Palson B, editors. Human cell culture, vol. 2. New York, NY: Kluwer Academic Publishers; 1999. p. 167–84.CrossRefGoogle Scholar
  57. 57.
    Hickey WF. Leukocyte traffic in the central nervous system: the participants and their roles. Semin Immunol. 1999;11(2):125–37.PubMedCrossRefGoogle Scholar
  58. 58.
    Decker WK, Xing D, Shpall EJ. Dendritic cell immunotherapy for the treatment of neoplastic disease. Biol Blood Marrow Transplant. 2006;12(2):113–25.PubMedCrossRefGoogle Scholar
  59. 59.
    Li Z, Lee JW, Mukherjee D, et al. Immunotherapy targeting glioma stem cells—insights and perspectives. Expert Opin Biol Ther. 2012;12(2):165–78.PubMedCrossRefGoogle Scholar
  60. 60.
    Yamanaka R, Itoh K. Peptide-based immunotherapeutic approaches to glioma: a review. Expert Opin Biol Ther. 2007;7:645–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Heimberger AB, Crotty LE, Archer GE, et al. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res. 2003;9(11):4247–54.PubMedGoogle Scholar
  62. 62.
    Debinski W, Gibo DM, Hulet SW, Connor JR, Gillespie GY. Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Clin Cancer Res. 1999;5(5):985–90.PubMedGoogle Scholar
  63. 63.
    Shimato S, Natsume A, Wakabayashi T, Tsujimura K, Nakahara N, Ishii J, Ito M, Akatsuka Y, Kuzushima K, Yoshida J. Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen. J Neurosurg. 2008;109(1):117–22.PubMedCrossRefGoogle Scholar
  64. 64.
    Oka Y, Elisseeva OA, Tsuboi A, Ogawa H, Tamaki H, Li H, Oji Y, Kim EH, Soma T, Asada M, Ueda K, Maruya E, Saji H, Kishimoto T, Udaka K, Sugiyama H. Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms’ tumor gene (WT1) product. Immunogenetics. 2000;51(2):99–107.PubMedCrossRefGoogle Scholar
  65. 65.
    Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol. 2008;116(1):79–86.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Okada H, Kalinski P, Ueda R, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with{α}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011;29(3):330–6.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Huang J, et al. Cytokine-induced killer (CIK) cells bound with anti-CD3/anti-CD133 bispecific antibodies target CD133(high) cancer stem cells in vitro and in vivo. Clin Immunol (Orlando, Fla). 2013;149(1):156–68.CrossRefGoogle Scholar
  68. 68.
    Ikegame A, et al. Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors. Leukemia. 2012;26(9):2124–34.PubMedCrossRefGoogle Scholar
  69. 69.
    Schlaak M, et al. Regression of metastatic melanoma in a patient by antibody targeting of cancer stem cells. Oncotarget. 2012;3(1):22–30.PubMedCentralPubMedGoogle Scholar
  70. 70.
    Ueda R, et al. Identification of HLA-A2- and A24-restricted T-cell epitopes derived from SOX6 expressed in glioma stem cells for immunotherapy. Int J Cancer. 2010;126(4):919–29.PubMedGoogle Scholar
  71. 71.
    Xu Q, et al. Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem Cells (Dayton, Ohio). 2009;27(8):1734–40.CrossRefGoogle Scholar
  72. 72.
    Xiao ZY, et al. An experimental study of dendritic cells transfected with cancer stem-like cells RNA against 9L brain tumors. Cancer Biol Ther. 2011;11(11):974–80. Web. 21 Mar. 2014.PubMedCrossRefGoogle Scholar
  73. 73.
    Pellegatta S, et al. Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas. Cancer Res. 2006;66(21):10247–52.PubMedCrossRefGoogle Scholar
  74. 74.
    Ning N, et al. Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res. 2012;72(7):1853–64. Web. 21 Mar. 2014.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Natsume A, et al. The DNA demethylating agent 5-aza-2′-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. Int J Cancer. 2008;122(11):2542–53. Web. 21 Mar. 2014.PubMedCrossRefGoogle Scholar
  76. 76.
    Odunsi K, et al. NY-ESO-1 and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer. Cancer Res. 2003;63(18):6076–83.PubMedGoogle Scholar
  77. 77.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA. Interleukin-2 or autologous lymphokine-activated killer cell treatment of malignant glioma: phase I trial. Cancer Res. 1986;46(4 Pt 2):2101–4.PubMedGoogle Scholar
  78. 78.
    Barba D, Saris SC, Holder C, Rosenberg SA, Oldfield EH. Intratumoral LAK cell and interleukin-2 therapy of human gliomas. J Neurosurg. 1989;70(2):175–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Blancher A, Roubinet F, Grancher AS, et al. Local immunotherapy of recurrent glioblastoma multiforme by intracerebral perfusion of interleukin-2 and LAK cells. Eur Cytokine Netw. 1993;4(5):331–41.PubMedGoogle Scholar
  80. 80.
    Boiardi A, Silvani A, Ruffini PA, et al. Loco-regional immunotherapy with recombinant interleukin-2 and adherent lymphokine-activated killer cells (A-LAK) in recurrent glioblastoma patients. Cancer Immunol Immunother. 1994;39(3):193–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Merchant RE, Grant AJ, Merchant LH, Young HF. Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2. Cancer. 1988;62(4):665–71.PubMedCrossRefGoogle Scholar
  82. 82.
    Merchant RE, Merchant LH, Cook SH, McVicar DW, Young HF. Intralesional infusion of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) for the treatment of patients with malignant brain tumor. Neurosurgery. 1988;23(6):725–32.PubMedCrossRefGoogle Scholar
  83. 83.
    Sankhla SK, Nadkarni JS, Bhagwati SN. Adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 for recurrent malignant primary brain tumors. J Neurooncol. 1996;27(2):133–40.PubMedCrossRefGoogle Scholar
  84. 84.
    Bielamowicz K, Khawja S, Ahmed N. Adoptive cell therapies for glioblastoma. Front Oncol. 2013;3:275.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Yoshida S, Tanaka R, Takai N, Ono K. Local administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 to patients with malignant brain tumors. Cancer Res. 1988;48(17):5011–6.PubMedGoogle Scholar
  86. 86.
    Okamoto Y, Shimizu K, Tamura K, et al. An adoptive immunotherapy of patients with medulloblastoma by lymphokine-activated killer cells (LAK). Acta Neurochir. 1988;94(1–2):47–52.PubMedCrossRefGoogle Scholar
  87. 87.
    Dillman RO, Duma CM, Schiltz PM, et al. Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma. J Immunother. 2004;27(5):398–404.PubMedCrossRefGoogle Scholar
  88. 88.
    Dillman RO, Duma CM, Ellis RA, et al. Intralesional lymphokine-activated killer cells as adjuvant therapy for primary glioblastoma. J Immunother. 2009;32(9):914–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Kitahara T, Watanabe O, Yamaura A, et al. Establishment of interleukin 2 dependent cytotoxic T lymphocyte cell line specific for autologous brain tumor and its intracranial administration for therapy of the tumor. J Neurooncol. 1987;4(4):329–36.PubMedCrossRefGoogle Scholar
  90. 90.
    Kruse CA, et al. Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2. Cancer Immunol Immunother. 1997;45(2):77–87.PubMedCrossRefGoogle Scholar
  91. 91.
    Tsuboi K, Saijo K, Ishikawa E, et al. Effects of local injection of ex vivo expanded autologous tumor-specific T lymphocytes in cases with recurrent malignant gliomas. Clin Cancer Res. 2003;9(9):3294–302.PubMedGoogle Scholar
  92. 92.
    Tsurushima H, Liu SQ, Tuboi K, et al. Reduction of end-stage malignant glioma by injection with autologous cytotoxic T lymphocytes. Jpn J Cancer Res. 1999;90(5):536–45.PubMedCrossRefGoogle Scholar
  93. 93.
    Quattrocchi KB, Miller CH, Cush S, et al. Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neurooncol. 1999;45(2):141–57.PubMedCrossRefGoogle Scholar
  94. 94.
    Holladay FP, Heitz-Turner T, Bayer WL, Wood GW. Autologous tumor cell vaccination combined with adoptive cellular immunotherapy in patients with Grade III/ IV astrocytoma. J Neurooncol. 1996;27(2):179–89.PubMedCrossRefGoogle Scholar
  95. 95.
    Plautz GE, Barnett GH, Miller DW, et al. Systemic T cell adoptive immunotherapy of malignant gliomas. J Neurosurg. 1998;89(1):42–51.PubMedCrossRefGoogle Scholar
  96. 96.
    Plautz GE, Miller DW, Barnett GH, et al. T cell adoptive immunotherapy of newly diagnosed gliomas. Clin Cancer Res. 2000;6(6):2209–18.PubMedGoogle Scholar
  97. 97.
    Sloan AE, Dansey R, Zamorano L, et al. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte–macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 2000;9(6):e9.PubMedCrossRefGoogle Scholar
  98. 98.
    Wood GW, Holladay FP, Turner T, Wang YY, Chiga M. A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent Grade III/IV astrocytoma. J Neurooncol. 2000;48(2):113–20.PubMedCrossRefGoogle Scholar
  99. 99.
    Kronik N, Kogan Y, Vainstein V, Agur Z. Improving alloreactive CTL immunotherapy for malignant gliomas using a simulation model of their interactive dynamics. Cancer Immunol Immunother. 2008;57(3):425–39.PubMedCrossRefGoogle Scholar
  100. 100.
    Mitchell DA, Xie W, Schmittling R, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol. 2008;10(1):10–8.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Cobbs CS, Harkins L, Samanta M, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62(12):3347–50.PubMedGoogle Scholar
  102. 102.
    Dziurzynski K, Wei J, Qiao W, et al. Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res. 2011;17(14):4642–9.PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Ishikawa E, Tsuboi K, Yamamoto T, et al. Clinical trial of autologous formalin-fixed tumor vaccine for glioblastoma multiforme patients. Cancer Sci. 2007;98(8):1226–33.PubMedCrossRefGoogle Scholar
  104. 104.
    Schneider T, Gerhards R, Kirches E, Firsching R. Preliminary results of active specific immunization with modified tumor cell vaccine in glioblastoma multiforme. J Neurooncol. 2001;53(1):39–46.PubMedCrossRefGoogle Scholar
  105. 105.
    Steiner HH, Bonsanto MM, Beckhove P, et al. Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit. J Clin Oncol. 2004;22(21):4272–81.PubMedCrossRefGoogle Scholar
  106. 106.
    Kikuchi T, Akasaki Y, Irie M, Homma S, Abe T, Ohno T. Results of a Phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother. 2001;50(7):337–44.PubMedCrossRefGoogle Scholar
  107. 107.
    Yu JS, et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial t-cell infiltration. Cancer Res. 2001;61(3):842–7.PubMedGoogle Scholar
  108. 108.
    Yu JS, Liu G, Ying H, Yong WH, Black KL, Wheeler CJ. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 2004;64(14):4973–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Wheeler CJ, Black KL, Liu G, et al. Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res. 2008;68(14):5955–64.PubMedCrossRefGoogle Scholar
  110. 110.
    Fadul CE, et al. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother (Hagerstown, Md 1997). 2011;34(4):382–9.CrossRefGoogle Scholar
  111. 111.
    Jie X, Hua L, Jiang W, Feng F, Feng G, Hua Z. Clinical application of a dendritic cell vaccine raised against heat-shocked glioblastoma. Cell Biochem Biophys. 2012;62(1):91–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Cho DY, Yang WK, Lee HC, et al. Adjuvant immunotherapy with whole-cell lysate dendritic cells vaccine for glioblastoma multiforme: a Phase II clinical trial. World Neurosurg. 2012;77(5–6):736–44.PubMedCrossRefGoogle Scholar
  113. 113.
    Westphal M, Ferdinand B. Final results of a randomized phase III trial of nimotuzumab for the treatment of newly diagnosed glioblastoma in addition to standard radiation and chemotherapy with temozolomide versus standard radiation and temoziolamide. J Clin Oncol. 2012;30(Suppl):abstr 2033. Web. 28 July 2014.Google Scholar
  114. 114.
    Wen PY, et al. A randomized, double-blind, placebo-controlled phase 2 trial of dendritic cell (DC) vaccination with ICT-107 in newly diagnosed glioblastoma (GBM) patients. J Clin Oncol. 2014;32(5s Suppl):abstr 2005. Web. 28 July 2014.Google Scholar
  115. 115.
    Yajima N, Yamanaka R, Mine T, et al. Immunologic evaluation of personalized peptide vaccination for patients with advanced malignant glioma. Clin Cancer Res. 2005;11(16):5900–11.PubMedCrossRefGoogle Scholar
  116. 116.
    Izumoto S, Tsuboi A, Oka Y, et al. Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme. J Neurosurg. 2008;108(5):963–71.PubMedCrossRefGoogle Scholar
  117. 117.
    Morita S, Oka Y, Tsuboi A, et al. A Phase I/II trial of a WT1 (Wilms’ tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the Phase I data. Jpn J Clin Oncol. 2006;36(4):231–6.PubMedCrossRefGoogle Scholar
  118. 118.
    Sampson JH, Aldape KD, Archer GE, et al. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro Oncol. 2011;13(3):324–33.PubMedCentralPubMedCrossRefGoogle Scholar
  119. 119.
    Sampson JH, Heimberger AB, Archer GE, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010;28(31):4722–9.PubMedCentralPubMedCrossRefGoogle Scholar
  120. 120.
    Crane CA, Han SJ, Ahn B, et al. Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein. Clin Cancer Res. 2013;19(1):205–14.PubMedCrossRefGoogle Scholar
  121. 121.
    Vik-Mo EO, Nyakas M, Mikkelsen BV, Moe MC, Due-Tønnesen P, Suso EM, Sæbøe-Larssen S, Sandberg C, Brinchmann JE, Helseth E, Rasmussen AM, Lote K, Aamdal S, Gaudernack G, Kvalheim G, Langmoen IA. Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother. 2013;62(9):1499–509.PubMedCentralPubMedCrossRefGoogle Scholar
  122. 122.
    Bigner DD, Brown M, Coleman RE, et al. Phase I studies of treatment of malignant gliomas and neoplastic meningitis with 131I-radiolabeled monoclonal antibodies anti-tenascin 81C6 and anti-chondroitin proteoglycan sulfate Me1-14F(ab′)2—a preliminary report. J Neurooncol. 1995;24(1):109–22.PubMedCrossRefGoogle Scholar
  123. 123.
    Kurpad SN, Zhao XG, Wikstrand CJ, Batra SK, McLendon RE, Bigner DD. Tumor antigens in astrocytic gliomas. Glia. 1995;15(3):244–56.PubMedCrossRefGoogle Scholar
  124. 124.
    Murphy-Ullrich JE, Lightner VA, Aukhil I, Yan YZ, Erickson HP, Hook M. Focal adhesion integrity is downregulated by the alternatively spliced domain of human tenascin. J Cell Biol. 1991;115(4):1127–36.PubMedCrossRefGoogle Scholar
  125. 125.
    Neyns B, Sadones J, Joosens E, et al. Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol. 2009;20(9):1596–603.PubMedCrossRefGoogle Scholar
  126. 126.
    Gil-gil JM, et al. Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol. 2013;7:123–35.PubMedCentralPubMedCrossRefGoogle Scholar
  127. 127.
    de Groot JF, Yung WK. Bevacizumab and irinotecan in the treatment of recurrent malignant gliomas. Cancer J. 2008;14(5):279–85.PubMedCrossRefGoogle Scholar
  128. 128.
    Lai A, Tran A, Nghiemphu PL, et al. Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol. 2011;29:142–8.PubMedCentralPubMedCrossRefGoogle Scholar
  129. 129.
    Gilbert MR, et al. RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). J Clin Oncol. 2013;31.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Mecca Madany
    • 1
    • 2
  • Tom M. Thomas
    • 1
    • 2
  • Lincoln Edwards
    • 1
  • John S. Yu
    • 1
    Email author
  1. 1.Maxine Dunitz Neurosurgical InstituteCedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Graduate Program in Biological Science & Translational MedicineCedars-Sinai Medical CenterLos AngelesUSA

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