Recent advances and future of immunotherapy for glioblastoma

Expert Opinion on Biological Therapy

Volumn 16, Issue 10, 2016, Pages 1245-1264

  Kamran, Neha ^a   Calinescu, Alexandra ^a   Candolfi, Marianela ^b   Chandran, Mayuri ^a   Mineharu, Yohei ^c   Asad, Antonela S ^b   Koschmann, Carl ^a   Nunez, Felipe J ^a   Lowenstein, Pedro R ^a   Castro, Maria G ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^c KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

cancer vaccines; checkpoint blockade; gene therapy; Glioma; immunotherapy; passive immunotherapy

Indexed keywords

ANTINEOPLASTIC AGENT; BETA INTERFERON; BEVACIZUMAB; BIOLOGICAL MARKER; CANCER VACCINE; CETUXIMAB; CHIMERIC ANTIGEN RECEPTOR; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; DENDRITIC CELL VACCINE; DNX 2401; EPHRIN RECEPTOR A2; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; ICT 107; IMMUNOLOGICAL ADJUVANT; INTERLEUKIN 13 RECEPTOR ALPHA2; INTERLEUKIN 2; INTERLEUKIN 4; IPILIMUMAB; LONTUCIREV; MONOCLONAL ANTIBODY; NIMOTUZUMAB; NIVOLUMAB; PEPTIDE VACCINE; RINDOPEPIMUT; SL 701; SURVIVIN; TEMOZOLOMIDE; TUMOR ANTIGEN; UNCLASSIFIED DRUG; VITESPEN;

ACTIVE IMMUNOTHERAPY; ADAPTIVE IMMUNITY; ADOPTIVE IMMUNOTHERAPY; ADOPTIVE TRANSFER; CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CANCER RECURRENCE; CELL THERAPY; DRUG TARGETING; GENE MUTATION; GENETIC HETEROGENEITY; GLIOBLASTOMA; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOMODULATORY GENE THERAPT; MOLECULAR BIOLOGY; NONHUMAN; ONCOLYTIC VIROTHERAPY; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PONTINE GLIOMA; PRECLINICAL STUDY; PROGRESSION FREE SURVIVAL; REVIEW; RISK REDUCTION; SUICIDE GENE THERAPY; T LYMPHOCYTE; TREATMENT OUTCOME; TUMOR MICROENVIRONMENT; ANIMAL; DRUG EFFECTS; FORECASTING; GENE THERAPY; GLIOMA; IMMUNOLOGY; IMMUNOTHERAPY; PASSIVE IMMUNIZATION; PROCEDURES; PROGNOSIS; TRENDS;

ANIMALS; FORECASTING; GENETIC THERAPY; GLIOBLASTOMA; GLIOMA; HUMANS; IMMUNIZATION, PASSIVE; IMMUNOTHERAPY; PROGNOSIS; TREATMENT OUTCOME; TUMOR MICROENVIRONMENT;

EID: 84985911238     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1080/14712598.2016.1212012     Document Type: Review

References (265)

1. D.N.Louis, H.Ohgaki, O.D.Wiestler, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007 Aug;114(2):97–109.
2. J.E.Eckel-Passow, D.H.Lachance, A.M.Molinaro, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015 Jun 25;372(26):2499–2508.
3. H.Suzuki, K.Aoki, K.Chiba, et al. Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet. 2015 May;47(5):458–468.
4. W.Paulus Pathology, molecular mechanisms and markers of gliomas:new insight and new challenges. Acta Neuropathol. 2015 Jun;129(6):773.
5. H.Yan, D.W.Parsons, G.Jin, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765–773.
6. Y.Jiao, P.J.Killela, Z.J.Reitman, et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget. 2012 Jul;3(7):709–722.
7. M.C.Chamberlain, D.Born. Prognostic significance of relative 1p/19q codeletion in oligodendroglial tumors. J Neuro Oncol. 2015 Nov;125(2):249–251.
8. C.Koschmann, A.A.Calinescu, F.J.Nunez, et al. ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Sci Transl Med. 2016 Mar 2;8(328):328ra28.
9. R.G.Verhaak, K.A.Hoadley, E.Purdom, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010 Jan 19;17(1):98–110.
10. E.G.Van Meir, C.G.Hadjipanayis, A.D.Norden, et al. Exciting new advances in neuro-oncology:the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010 May–Jun;60(3):166–193.
11. P.Jha, V.Suri, G.Singh, et al. Characterization of molecular genetic alterations in GBMs highlights a distinctive molecular profile in young adults. Diagnostic Mol Pathol. 2011 Dec;20(4):225–232.
12. H.Ohgaki, P.Kleihues. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013 Feb 15;19(4):764–772.
13. A.M.Fontebasso, X.Y.Liu, D.Sturm, et al. Chromatin remodeling defects in pediatric and young adult glioblastoma:a tale of a variant histone 3 tail. Brain Pathol. 2013 Mar;23(2):210–216.
14. D.Sturm, H.Witt, V.Hovestadt, et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell. 2012 Oct 16;22(4):425–437.
15. A.M.Lindroth, C.Plass. Recurrent H3.3 alterations in childhood tumors. Nat Genet. 2013 Dec;45(12):1413–1414.
16. R.Stupp, W.P.Mason, M.J.van den Bent, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987–996.
17. M.Lacroix, D.Abi-Said, D.R.Fourney, et al. A multivariate analysis of 416 patients with glioblastoma multiforme:prognosis, extent of resection, and survival. J Neurosurg. 2001 Aug;95(2):190–198.
18. J.S.Smith, E.F.Chang, K.R.Lamborn, et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol. 2008 Mar 10;26(8):1338–1345.
19. K.Abhinav, F.C.Yeh, A.Mansouri, et al. High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery. Neuro Oncol. 2015 Sep;17(9):1199–1209.
20. M.D.Chan. Recent technical advances and indications for radiation therapy in low-grade glioma. Semin Radiat Oncol. 2015 Jul;25(3):189–196.
21. M.J.van den Bent, H.J.Dubbink, M.Sanson, et al. MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors:a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol. 2009 Dec 10;27(35):5881–5886.
22. S.Agarwal, P.Manchanda, M.A.Vogelbaum, et al. Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells:findings in an orthotopic rat xenograft model of glioma. Drug Metab Dispos. 2013 Jan;41(1):33–39.
23. C.M.Jackson, M.Lim, C.G.Drake. Immunotherapy for brain cancer:recent progress and future promise. Clin Cancer Res. 2014 Jul 15;20(14):3651–3659.
24. A.A.Calinescu, N.Kamran, G.Baker, et al. Overview of current immunotherapeutic strategies for glioma. Immunotherapy. 2015;7(10):1073–1104.
25. D.A.Reardon, G.Freeman, C.Wu, et al. Immunotherapy advances for glioblastoma. Neuro Oncol. 2014 Nov;16(11):1441–1458.
26. E.S.Kim, J.E.Kim, M.A.Patel, et al. Immune checkpoint modulators:an emerging antiglioma armamentarium. J Immunol Res. 2016;2016:4683607.• Describes Phase 1 clinical trial results of DC vaccination with autologous tumor peptides; vaccination induced systemic and intracranial T cell response, but this response was limited by active tumor progression and TGF-B2 expression.
27. J.Galon, H.K.Angell, D.Bedognetti, et al. The continuum of cancer immunosurveillance:prognostic, predictive, and mechanistic signatures. Immunity. 2013 Jul 25;39(1):11–26.
28. T.F.Gajewski, S.R.Woo, Y.Zha, et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol. 2013 Apr;25(2):268–276.
29. J.E.Kim, M.Lim. The role of checkpoints in the treatment of GBM. J Neuro Oncol. 2015 Jul;123(3):413–423.
30. J.Goldmann, E.Kwidzinski, C.Brandt, et al. T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa. J Leukoc Biol. 2006 Oct;80(4):797–801.
31. H.F.Cserr, C.J.Harling-Berg, P.M.Knopf. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 1992 Oct;2(4):269–276.
32. D.C.Davies. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat. 2002 Jun;200(6):639–646.
33. L.M.Liau, R.M.Prins, S.M.Kiertscher, et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005 Aug 1;11(15):5515–5525.
34. J.H.Sampson, K.D.Aldape, G.E.Archer, et al. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro Oncol. 2011 Mar;13(3):324–333.
35. A.B.Heimberger, L.Y.Kong, M.Abou-Ghazal, et al. The role of tregs in human glioma patients and their inhibition with a novel STAT-3 inhibitor. Clin Neurosurg. 2009;56:98–106.
36. J.G.Zhang, C.A.Kruse, L.Driggers, et al. Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy. J Neuro Oncol. 2008 May;88(1):65–76.
37. S.A.Grossman, X.Ye, G.Lesser, et al. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res. 2011 Aug 15;17(16):5473–5480.
38. S.M.Razavi, K.E.Lee, B.E.Jin, et al. Immune evasion strategies of glioblastoma. Front Surg. 2016;3:11.
39. J.T.Jordan, W.Sun, S.F.Hussain, et al. Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunol Immunother. 2008 Jan;57(1):123–131.
40. O.Bloch, C.A.Crane, R.Kaur, et al. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013 Jun 15;19(12):3165–3175.•• This review summarizes the role of CTLA-4 in negatively regulating T cell response and demonstrates the potential of CTLA-4 as an immunotherapeutic target.
41. D.I.Gabrilovich, S.Nagaraj. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009 Mar;9(3):162–174.•• Demonstrates the ability of CTLA-4 blockade to produce synergistic antitumor activity through enhancement of effector T cell function and inhibition of regulatory T cell function.
42. A.Facoetti, R.Nano, P.Zelini, et al. Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin Cancer Res. 2005 Dec 1;11(23):8304–8311.
43. L.Kren, O.Slaby, K.Muckova, et al. Expression of immune-modulatory molecules HLA-G and HLA-E by tumor cells in glioblastomas:an unexpected prognostic significance? Neuropathology. 2011 Apr;31(2):129–134.
44. I.J.Wastowski, R.T.Simoes, L.Yaghi, et al. Human leukocyte antigen-G is frequently expressed in glioblastoma and may be induced in vitro by combined 5-aza-2ʹ-deoxycytidine and interferon-gamma treatments:results from a multicentric study. Am J Pathol. 2013 Feb;182(2):540–552.
45. L.W.Xu, K.K.Chow, M.Lim, et al. Current vaccine trials in glioblastoma:a review. J Immunol Res. 2014;2014:796856.
46. B.Badie, J.Schartner, S.Prabakaran, et al. Expression of Fas ligand by microglia:possible role in glioma immune evasion. J Neuroimmunol. 2001 Nov 1;120(1–2):19–24.
47. J.G.Egen, M.S.Kuhns, J.P.Allison. CTLA-4:new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002 Jul;3(7):611–618.
48. K.S.Peggs, S.A.Quezada, C.A.Chambers, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med. 2009 Aug 3;206(8):1717–1725.
49. A.A.Tarhini, J.M.Kirkwood. CTLA-4-blocking immunotherapy with ipilimumab for advanced melanoma. Oncology (Williston Park). 2010 Dec;24(14):1302, 04.
50. D.M.Pardoll. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Apr;12(4):252–264.
51. J.F.Grosso, C.C.Kelleher, T.J.Harris, et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest. 2007 Nov;117(11):3383–3392.
52. A.S.Berghoff, B.Kiesel, G.Widhalm, et al. Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol. 2015 Aug;17(8):1064–1075.
53. Z.Liu, H.Han, X.He, et al. Expression of the galectin-9-Tim-3 pathway in glioma tissues is associated with the clinical manifestations of glioma. Oncol Lett. 2016 Mar;11(3):1829–1834.
54. D.S.Chen, I.Mellman. Oncology meets immunology:the cancer-immunity cycle. Immunity. 2013 Jul 25;39(1):1–10.•• Summarizes the interactions of CD28 and CTLA-4 with B7/BB1 and describes the role of these signaling pathways in IL-2 production and T cell activation.
55. G.Driessens, J.Kline, T.F.Gajewski. Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev. 2009 May;229(1):126–144.•• Demonstrates that B7-1 (CD80) and B7-2 (CD86) show similar overall receptor binding and T cell costimulatory properties, but B7-1 binds CTLA4 more readily and dissociates from CTLA-4 more slowly than B7-2.
56. C.Jackson, J.Ruzevick, J.Phallen, et al. Challenges in immunotherapy presented by the glioblastoma multiforme microenvironment. Clin Dev Immunol. 2011;2011:732413.
57. S.Saikali, T.Avril, B.Collet, et al. Expression of nine tumour antigens in a series of human glioblastoma multiforme:interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy. J Neuro Oncol. 2007 Jan;81(2):139–148.•• Demonstrates the activity of ipilimumab in patients with advanced melanoma and brain metastases, and shows that ipilimumab does not produce unexpected adverse effects in this population.
58. G.Bakdash, S.P.Sittig, T.van Dijk, et al. The nature of activatory and tolerogenic dendritic cell-derived signal II. Front Immunol. 2013;4:53.
59. N.Joller, J.P.Hafler, B.Brynedal, et al. Cutting edge:TIGIT has T cell-intrinsic inhibitory functions. J Immunol. 2011 Feb 1;186(3):1338–1342.
60. W.D.Hastings, D.E.Anderson, N.Kassam, et al. TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. Eur J Immunol. 2009 Sep;39(9):2492–2501.
61. R.H.Schwartz. Costimulation of T lymphocytes:the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992 Dec 24;71(7):1065–1068.
62. P.S.Linsley, J.L.Greene, W.Brady, et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity. 1994 Dec;1(9):793–801.
63. F.S.Hodi, S.J.O’Day, D.F.McDermott, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711–723.
64. K.Margolin, M.S.Ernstoff, O.Hamid, et al. Ipilimumab in patients with melanoma and brain metastases:an open-label, phase 2 trial. Lancet Oncol. 2012 May;13(5):459–465.
65. P.Queirolo, F.Spagnolo, P.A.Ascierto, et al. Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases. J Neuro Oncol. 2014 May;118(1):109–116.
66. Company B-MS. Yervoy (ipilimumab) [prescribing information]. [cited 2013]. Available from: http://www.yervoy.com.
67. P.E.Fecci, H.Ochiai, D.A.Mitchell, et al. Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function. Clin Cancer Res. 2007 Apr 1;13(7):2158–2167.
68. J.Vom Berg, M.Vrohlings, S.Haller, et al. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection. J Exp Med. 2013 Dec 16;210(13):2803–2811.
69. P.Agarwalla, Z.Barnard, P.Fecci, et al. Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors. J Immunother. 2012 Jun;35(5):385–389.
70. S.L.Topalian, F.S.Hodi, J.R.Brahmer, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443–2454.
71. M.J.Eppihimer, J.Gunn, G.J.Freeman, et al. Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation. 2002 Apr;9(2):133–145.
72. Y.Liu, R.Carlsson, M.Ambjorn, et al. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients. J Neurosci. 2013 Aug 28;33(35):14231–14245.• Summarizes preclinical and clinical studies of immune checkpoint modulators in glioblastoma and outlines specific challenges in clinical development of checkpoint modulators.
73. J.D.Wolchok, H.Kluger, M.K.Callahan, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013 Jul 11;369(2):122–133.
74. J.S.Weber, R.R.Kudchadkar, B.Yu, et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013 Dec 1;31(34):4311–4318.
75. Company B-MS. Opdivo (nivolumab) [prescribing information]. [cited 2014]. Available from: http://www.opdivo.bmscustomerconnect.com/gateway.
76. Merck & Co. I. Keytruda (pembrolizumab) [prescribing information]. [cited 2015]. Available from: http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf.
77. S.M.Ansell, A.M.Lesokhin, I.Borrello, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015 Jan 22;372(4):311–319.
78. J.A.Scott. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC:Interim phase I results. J Clin Oncol. 2016 Jun 27. pii:JCO669861. [Epub ahead of print].
79. M.Preusser, M.Lim, D.A.Hafler, et al. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nat Rev Neurol. 2015 Sep;11(9):504–514.• Reports preclinical evidence that combinatorial blockade of IDO, CTLA-4, and PDL-1 in mouse models of GBM decreases tumor-infiltrating regulatory T cells and mediates long term survival.
80. D.A.Hafler, V.Kuchroo. TIMs:central regulators of immune responses. J Exp Med. 2008 Nov 24;205(12):2699–2701.
81. A.C.Anderson. Tim-3:an emerging target in the cancer immunotherapy landscape. Cancer Immunol Res. 2014 May;2(5):393–398.
82. S.Han, S.Feng, L.Xu, et al. Tim-3 on peripheral CD4(+) and CD8(+) T cells is involved in the development of glioma. DNA Cell Biol. 2014 Apr;33(4):245–250.
83. J.Zeng, A.P.See, J.Phallen, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):343–349.
84. C.Uyttenhove, L.Pilotte, I.Theate, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003 Oct;9(10):1269–1274.
85. D.A.Wainwright, I.V.Balyasnikova, A.L.Chang, et al. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin Cancer Res. 2012 Nov 15;18(22):6110–6121.
86. D.A.Wainwright, A.L.Chang, M.Dey, et al. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors. Clin Cancer Res. 2014 Oct 15;20(20):5290–5301.• Summarizes mechanisms which regulate immunogenicity of dying cancer cells.
87. E.Baixeras, B.Huard, C.Miossec, et al. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med. 1992 Aug 1;176(2):327–337.•• Describes a novel mechanism of anti-GBM immune stimulation through TLR2 signaling mediated by release of HMGB1 by dying tumor cells.
88. S.R.Woo, M.E.Turnis, M.V.Goldberg, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012 Feb 15;72(4):917–927.
89. S.Grossauer, K.Koeck, C.Petritsch. Immunecheckpoint blockage - a promising strategy to overcome glioma stem cell therapy-resistance. Insights Neurosurg. 2016;1(1):1.
90. M.G.Castro, M.Candolfi, T.J.Wilson, et al. Adenoviral vector-mediated gene therapy for gliomas:coming of age. Expert Opin Biol Ther. 2014 Sep;14(9):1241–1257.
91. J.R.Kane, J.Miska, J.S.Young, et al. Sui generis:gene therapy and delivery systems for the treatment of glioblastoma. Neuro Oncol. 2015 Mar;17(Suppl 2):ii24–ii36.
92. S.T.Workenhe, K.L.Mossman. Oncolytic virotherapy and immunogenic cancer cell death:sharpening the sword for improved cancer treatment strategies. Mol Ther. 2014 Feb;22(2):251–256.
93. D.V.Krysko, A.D.Garg, A.Kaczmarek, et al. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012 Dec;12(12):860–875.
94. J.F.Curtin, N.Liu, M.Candolfi, et al. HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med. 2009 Jan 13;6(1):e10.
95. S.Duarte, G.Carle, H.Faneca, et al. Suicide gene therapy in cancer:where do we stand now? Cancer Lett. 2012 Nov 28;324(2):160–170.
96. H.Okura, C.Smith, J.Rutka. Gene therapy for malignant glioma. Mol Cell Ther. 2014;2(1):1–19. Epub 2014 Jul 08.•• Demonstrates the requirement of tumor cell killing through HSV1-TK therapy combined with immunostimulation through Flt3L to produce an effective anti-glioma response.
97. A.Tobias, A.Ahmed, K.S.Moon, et al. The art of gene therapy for glioma:a review of the challenging road to the bedside. J Neurol Neurosurg Psychiatry. 2013 Feb;84(2):213–222.
98. M.D.Prados, M.McDermott, S.M.Chang, et al. Treatment of progressive or recurrent glioblastoma multiforme in adults with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration:a phase I/II multi-institutional trial. J Neuro Oncol. 2003 Dec;65(3):269–278.
99. I.M.Germano, L.Emdad, Z.A.Qadeer, et al. Embryonic stem cell (ESC)-mediated transgene delivery induces growth suppression, apoptosis and radiosensitization, and overcomes temozolomide resistance in malignant gliomas. Cancer Gene Ther. 2010 Sep;17(9):664–674.
100. N.G.Rainov. A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther. 2000 Nov 20;11(17):2389–2401.
101. E.Maraskovsky, K.Brasel, M.Teepe, et al. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice:multiple dendritic cell subpopulations identified. J Exp Med. 1996 Nov 1;184(5):1953–1962.
102. S.Ali, J.F.Curtin, J.M.Zirger, et al. Inflammatory and anti-glioma effects of an adenovirus expressing human soluble Fms-like tyrosine kinase 3 ligand (hsFlt3L):treatment with hsFlt3L inhibits intracranial glioma progression. Mol Ther. 2004 Dec;10(6):1071–1084.
103. S.Ali, G.D.King, J.F.Curtin, et al. Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model. Cancer Res. 2005 Aug 15;65(16):7194–7204.
104. M.Candolfi, J.F.Curtin, K.Yagiz, et al. B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma. Neoplasia. 2011 Oct;13(10):947–960.
105. G.D.King, A.K.Muhammad, J.F.Curtin, et al. Flt3L and TK gene therapy eradicate multifocal glioma in a syngeneic glioblastoma model. Neuro Oncol. 2008 Feb;10(1):19–31.
106. G.D.King, A.K.Muhammad, D.Larocque, et al. Combined Flt3L/TK gene therapy induces immunological surveillance which mediates an immune response against a surrogate brain tumor neoantigen. Mol Ther. 2011 Oct;19(10):1793–1801.
107. M.Aghi, R.L.Martuza. Oncolytic viral therapies - the clinical experience. Oncogene. 2005 Nov 21;24(52):7802–7816.
108. K.A.Cassady, J.N.Parker. Herpesvirus vectors for therapy of brain tumors. Open Virol J. 2010;4:103–108.
109. R.Myers, M.Harvey, T.J.Kaufmann, et al. Toxicology study of repeat intracerebral administration of a measles virus derivative producing carcinoembryonic antigen in rhesus macaques in support of a phase I/II clinical trial for patients with recurrent gliomas. Hum Gene Ther. 2008 Jul;19(7):690–698.
110. P.Forsyth, G.Roldan, D.George, et al. A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Mol Ther. 2008 Mar;16(3):627–632.
111. J.W.Kim, J.R.Kane, J.S.Young, et al. A genetically modified adenoviral vector with a phage display-derived peptide incorporated into fiber fibritin chimera prolongs survival in experimental glioma. Hum Gene Ther. 2015 Sep;26(9):635–646.
112. S.Nandi, I.V.Ulasov, M.A.Tyler, et al. Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells. Cancer Res. 2008 Jul 15;68(14):5778–5784.
113. D.Kirn, T.Hermiston, F.McCormick. ONYX-015:clinical data are encouraging. Nat Med. 1998 Dec;4(12):1341–1342.
114. E.A.Chiocca, K.M.Abbed, S.Tatter, et al. A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther. 2004 Nov;10(5):958–966.
115. F.F.Lang, C.Conrad, C.Gomez-Manzano, et al. First-in-human phase I clinical trial of oncolytic delta-24-RGD (DNX-2401) with biological endpoints:implications for viro- immunotherapy. Neuro Oncol. 2014 July 1;16(suppl3):iii39.
116. S.K.Jacobs, D.J.Wilson, P.L.Kornblith, et al. Interleukin-2 or autologous lymphokine-activated killer cell treatment of malignant glioma:phase I trial. Cancer Res. 1986 Apr;46(4 Pt 2):2101–2104.
117. F.P.Holladay, T.Heitz-Turner, W.L.Bayer, et al. Autologous tumor cell vaccination combined with adoptive cellular immunotherapy in patients with grade III/IV astrocytoma. J Neuro Oncol. 1996 Feb;27(2):179–189.
118. F.Colombo, L.Barzon, E.Franchin, et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme:biological and clinical results. Cancer Gene Ther. 2005 Oct;12(10):835–848.
119. H.Okada, K.M.Giezeman-Smits, H.Tahara, et al. Effective cytokine gene therapy against an intracranial glioma using a retrovirally transduced IL-4 plus HSVtk tumor vaccine. Gene Ther. 1999 Feb;6(2):219–226.
120. H.Okada, I.F.Pollack, M.T.Lotze, et al. Gene therapy of malignant gliomas:a phase I study of IL-4-HSV-TK gene-modified autologous tumor to elicit an immune response. Hum Gene Ther. 2000 Mar 1;11(4):637–653.
121. A.Natsume, D.Ishii, T.Wakabayashi, et al. IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide. Cancer Res. 2005 Sep 1;65(17):7573–7579.• Presents a novel IDH1 peptide vaccine which induces antigen-specific T cell response and tumor control in mouse models.
122. A.Natsume, T.Wakabayashi, D.Ishii, et al. A combination of IFN-beta and temozolomide in human glioma xenograft models:implication of p53-mediated MGMT downregulation. Cancer Chemother Pharmacol. 2008 Apr;61(4):653–659.
123. T.Wakabayashi, A.Natsume, Y.Hashizume, et al. A phase I clinical trial of interferon-beta gene therapy for high-grade glioma:novel findings from gene expression profiling and autopsy. J Gene Med. 2008 Apr;10(4):329–339.
124. E.A.Chiocca, K.M.Smith, B.McKinney, et al. A phase I trial of Ad.hIFN-beta gene therapy for glioma. Mol Ther. 2008 Mar;16(3):618–626.
125. T.N.Schumacher, R.D.Schreiber. Neoantigens in cancer immunotherapy. Science. 2015 Apr 3;348(6230):69–74.
126. B.Heemskerk, P.Kvistborg, T.N.Schumacher. The cancer antigenome. EMBO J. 2013 Jan 23;32(2):194–203.
127. A.B.Heimberger, D.Suki, D.Yang, et al. The natural history of EGFR and EGFRvIII in glioblastoma patients. J Transl Med. 2005 Oct;19(3):38.
128. G.Liu, X.Yuan, Z.Zeng, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer. 2006;5:67.
129. S.Phuphanich, C.J.Wheeler, J.D.Rudnick, et al. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2013 Jan;62(1):125–135.
130. G.Liu, J.S.Yu, G.Zeng, et al. AIM-2:a novel tumor antigen is expressed and presented by human glioma cells. J Immunother. 2004 May-Jun;27(3):220–226.
131. J.G.Zhang, J.Eguchi, C.A.Kruse, et al. Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):566–575.• Reports antigen-specific immune response and clinical response in children with malignant gliomas vaccinated with the combinatorial peptide vaccine containing EphA2, IL-13Rα2, and survivin peptides.
132. G.R.Sareddy, M.Panigrahi, S.Challa, et al. Activation of Wnt/beta-catenin/Tcf signaling pathway in human astrocytomas. Neurochem Int. 2009 Sep;55(5):307–317.
133. C.Liu, Y.Tu, X.Sun, et al. Wnt/beta-Catenin pathway in human glioma:expression pattern and clinical/prognostic correlations. Clin Exp Med. 2011 Jun;11(2):105–112.
134. T.Cenci, M.Martini, N.Montano, et al. Prognostic relevance of c-Myc and BMI1 expression in patients with glioblastoma. Am J Clin Pathol. 2012 Sep;138(3):390–396.
135. C.Leung, M.Lingbeek, O.Shakhova, et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature. 2004 Mar 18;428(6980):337–341.
136. M.Zakrzewska, K.Zakrzewski, S.M.Gresner, et al. Polycomb genes expression as a predictor of poor clinical outcome in children with medulloblastoma. Child’s Nerv Syst. 2011 Jan;27(1):79–86.
137. K.Allan, R.C.Jordan, L.C.Ang, et al. Overexpression of cyclin A and cyclin B1 proteins in astrocytomas. Arch Pathol Lab Med. 2000 Feb;124(2):216–220.
138. S.A.Rempel, M.L.Rosenblum, T.Mikkelsen, et al. Cathepsin B expression and localization in glioma progression and invasion. Cancer Res. 1994 Dec 1;54(23):6027–6031.
139. S.Gopinath, R.Malla, K.Alapati, et al. Cathepsin B and uPAR regulate self-renewal of glioma-initiating cells through GLI-regulated Sox2 and Bmi1 expression. Carcinogenesis. 2013 Mar;34(3):550–559.
140. M.Sivaparvathi, R.Sawaya, S.W.Wang, et al. Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis. 1995 Jan;13(1):49–56.
141. V.Barresi, F.R.Buttarelli, E.E.Vitarelli, et al. Caveolin-1 expression in diffuse gliomas:correlation with the proliferation index, epidermal growth factor receptor, p53, and 1p/19q status. Hum Pathol. 2009 Dec;40(12):1738–1746.
142. R.Senetta, C.Miracco, S.Lanzafame, et al. Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes. Neuro Oncol. 2011 Feb;13(2):176–183.
143. S.K.Singh, I.D.Clarke, M.Terasaki, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003 Sep 15;63(18):5821–5828.
144. D.R.Emlet, P.Gupta, M.Holgado-Madruga, et al. Targeting a glioblastoma cancer stem-cell population defined by EGF receptor variant III. Cancer Res. 2014 Feb 15;74(4):1238–1249.•• Demonstrates the ability of vaccine site preconditioning with tetanus toxoid to enhance DC migration and improve survival in GBM patients.
145. R.H.Dahlrot, S.Hansen, S.S.Jensen, et al. Clinical value of CD133 and nestin in patients with glioma:a population-based study. Int J Clin Exp Pathol. 2014;7(7):3739–3751.
146. M.Zhang, T.Song, L.Yang, et al. Nestin and CD133:valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res. 2008;27:85.
147. G.J.Kitange, B.L.Carlson, M.A.Schroeder, et al. Expression of CD74 in high grade gliomas:a potential role in temozolomide resistance. J Neuro Oncol. 2010 Nov;100(2):177–186.
148. N.Baron, O.Deuster, C.Noelker, et al. Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells. J Neurosci Res. 2011 May;89(5):711–717.
149. T.Shono, P.J.Tofilon, J.M.Bruner, et al. Cyclooxygenase-2 expression in human gliomas:prognostic significance and molecular correlations. Cancer Res. 2001 Jun 1;61(11):4375–4381.
150. M.Penas-Prado, K.R.Hess, M.J.Fisch, et al. Randomized phase II adjuvant factorial study of dose-dense temozolomide alone and in combination with isotretinoin, celecoxib, and/or thalidomide for glioblastoma. Neuro Oncol. 2015 Feb;17(2):266–273.
151. S.Eberstal, W.Badn, S.Fritzell, et al. Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors. Cancer Immunol Immunother. 2012 Aug;61(8):1191–1199.
152. L.J.Lewis-Tuffin, F.Rodriguez, C.Giannini, et al. Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype. Plos One. 2010;5(10):e13665.
153. W.Wu, Y.Tian, H.Wan, et al. Expression of beta-catenin and E- and N-cadherin in human brainstem gliomas and clinicopathological correlations. Int J Neurosci. 2013 May;123(5):318–323.
154. J.H.Sampson, A.B.Heimberger, G.E.Archer, 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 Nov 1;28(31):4722–4729.
155. R.Babu, D.C.Adamson. Rindopepimut:an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma. Core Evid. 2012;7:93–103.
156. J.Schuster, R.K.Lai, L.D.Recht, et al. A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma:the ACT III study. Neuro Oncol. 2015 Jan;17(6):854–861.
157. A.B.Heimberger, J.H.Sampson. The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients. Expert Opin Biol Ther. 2009 Aug;9(8):1087–1098.
158. H.Okada, P.Kalinski, R.Ueda, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011 Jan 20;29(3):330–336.
159. J.Wykosky, D.M.Gibo, C.Stanton, et al. Interleukin-13 receptor alpha 2, EphA2, and Fos-related antigen 1 as molecular denominators of high-grade astrocytomas and specific targets for combinatorial therapy. Clin Cancer Res. 2008 Jan 1;14(1):199–208.
160. H.Okada, G.Kohanbash, X.Zhu, et al. Immunotherapeutic approaches for glioma. Crit Rev Immunol. 2009;29(1):1–42.
161. L.Driggers, J.G.Zhang, E.W.Newcomb, et al. Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy:a medical hypothesis paper. J Neuro Oncol. 2010 Apr;97(2):159–169.
162. R.Ueda, K.L.Low, X.Zhu, et al. Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma. J Transl Med. 2007;5:68.
163. I.F.Pollack, R.I.Jakacki, L.H.Butterfield, et al. Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomas. J Clin Oncol. 2014 Jul 1;32(19):2050–2058.
164. F.Orzan, S.Pellegatta, P.L.Poliani, et al. Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells. Neuropathol Appl Neurobiol. 2011 Jun;37(4):381–394.
165. D.L.Scarcella, C.W.Chow, M.F.Gonzales, et al. Expression of MAGE and GAGE in high-grade brain tumors:a potential target for specific immunotherapy and diagnostic markers. Clin Cancer Res. 1999 Feb;5(2):335–341.
166. H.D.Mennel, B.Lell. Ganglioside (GD2) expression and intermediary filaments in astrocytic tumors. Clin Neuropathol. 2005 Jan-Feb;24(1):13–18.
167. G.Schulz, D.A.Cheresh, N.M.Varki, et al. Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res. 1984 Dec;44(12 Pt 1):5914–5920.
168. G.Finocchiaro, S.Pellegatta. Immunotherapy with dendritic cells loaded with glioblastoma stem cells:from preclinical to clinical studies. Cancer Immunol Immunother. 2016 Jan;65(1):101–109.
169. G.Cantini, F.Pisati, S.Pessina, et al. Immunotherapy against the radial glia marker GLAST effectively triggers specific antitumor effectors without autoimmunity. Oncoimmunology. 2012 Sep 1;1(6):884–893.
170. A.Jimeno, G.J.Weiss, W.H.MillerJr., et al. Phase I study of the hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors. Clin Cancer Res. 2013 May 15;19(10):2766–2774.
171. D.Cui, Q.Xu, K.Wang, et al. Gli1 is a potential target for alleviating multidrug resistance of gliomas. J Neurol Sci. 2010 Jan 15;288(1–2):156–166.
172. M.Rossi, L.Magnoni, C.Miracco, et al. beta-catenin and Gli1 are prognostic markers in glioblastoma. Cancer Biol Ther. 2011 Apr 15;11(8):753–761.
173. H.Yamamoto, J.Swoger, S.Greene, et al. Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas:implications for a role in regulating invasivity. Cancer Res. 2000 Jan 1;60(1):134–142.
174. Y.Akiyama, C.Oshita, A.Kume, et al. Alpha-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma:a phase I clinical trial. BMC Cancer. 2012;12:623.
175. G.Liu, H.Ying, G.Zeng, et al. HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by cytotoxic T cells. Cancer Res. 2004 Jul 15;64(14):4980–4986.
176. Q.Xu, G.Liu, X.Yuan, et al. Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem Cells. 2009 Aug;27(8):1734–1740.
177. M.S.Waitkus, B.H.Diplas, H.Yan. Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol. 2016 Jan;18(1):16–26.
178. D.A.Mitchell, X.Cui, R.J.Schmittling, et al. Monoclonal antibody blockade of IL-2 receptor alpha during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood. 2011 Sep 15;118(11):3003–3012.
179. A.Mintz, D.M.Gibo, B.Slagle-Webb, et al. IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13. Neoplasia. 2002 Sep-Oct;4(5):388–399.•• Defines three subgroups of GBM based on H3F3A and IDH1 mutation which display distinct epigenetic and anatomic characteristics.
180. M.Kogiku, I.Ohsawa, K.Matsumoto, et al. Prognosis of glioma patients by combined immunostaining for survivin, Ki-67 and epidermal growth factor receptor. J Clin Neurosci. 2008 Nov;15(11):1198–1203.
181. O.Persson, L.G.Salford, J.Fransson, et al. Distribution, cellular localization, and therapeutic potential of the tumor-associated antigen Ku70/80 in glioblastoma multiforme. J Neuro Oncol. 2010 Apr;97(2):207–215.
182. S.Bao, Q.Wu, Z.Li, et al. Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 2008 Aug 1;68(15):6043–6048.
183. L.Cheng, Q.Wu, Z.Huang, et al. L1CAM regulates DNA damage checkpoint response of glioblastoma stem cells through NBS1. EMBO J. 2011 Mar 2;30(5):800–813.
184. L.Bao, K.Dunham, K.Lucas. MAGE-A1, MAGE-A3, and NY-ESO-1 can be upregulated on neuroblastoma cells to facilitate cytotoxic T lymphocyte-mediated tumor cell killing. Cancer Immunol Immunother. 2011 Sep;60(9):1299–1307.
185. C.T.Kuan, N.Srivastava, R.E.McLendon, et al. Recombinant single-chain variable fragment antibodies against extracellular epitopes of human multidrug resistance protein MRP3 for targeting malignant gliomas. Int J Cancer. 2010 Aug 1;127(3):598–611.
186. M.Terasaki, S.Shibui, Y.Narita, et al. Phase I trial of a personalized peptide vaccine for patients positive for human leukocyte antigen–A24 with recurrent or progressive glioblastoma multiforme. J Clin Oncol. 2011 January 20;29(3):337–344.
187. T.Ishiwata, K.Teduka, T.Yamamoto, et al. Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas. Oncol Rep. 2011 Jul;26(1):91–99.
188. M.V.Dhodapkar, M.Sznol, B.Zhao, et al. Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci Transl Med. 2014 Apr 16;6(232):232–251.
189. A.Rousseau, C.L.Nutt, R.A.Betensky, et al. Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas:use of YKL-40, ApoE, ASCL1, and NKX2-2. J Neuropathol Exp Neurol. 2006 Dec;65(12):1149–1156.
190. K.L.Ligon, E.Huillard, S.Mehta, et al. Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron. 2007 Feb 15;53(4):503–517.
191. K.L.Ligon, J.A.Alberta, A.T.Kho, et al. The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol. 2004 May;63(5):499–509.
192. T.Elsir, A.Eriksson, A.Orrego, et al. Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas. J Neuropathol Exp Neurol. 2010 Feb;69(2):129–138.
193. K.D.Geiger, S.Hendruschk, E.P.Rieber, et al. The prostate stem cell antigen represents a novel glioma-associated antigen. Oncol Rep. 2011 Jul;26(1):13–21.
194. M.Schmitz, A.Temme, V.Senner, et al. Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy. Br J Cancer. 2007 Apr 23;96(8):1293–1301.
195. R.Favaro, I.Appolloni, S.Pellegatta, et al. Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma. Cancer Res. 2014 Mar 15;74(6):1833–1844.
196. R.Ueda, K.Ohkusu-Tsukada, N.Fusaki, 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 Feb 15;126(4):919–929.
197. M.Schmitz, R.Wehner, S.Stevanovic, et al. Identification of a naturally processed T cell epitope derived from the glioma-associated protein SOX11. Cancer Lett. 2007 Jan 8;245(1–2):331–336.
198. M.J.Son, K.Woolard, D.H.Nam, et al. SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell. 2009 May 8;4(5):440–452.
199. A.Tchirkov, C.Rolhion, J.L.Kemeny, et al. Clinical implications of quantitative real-time RT-PCR analysis of hTERT gene expression in human gliomas. Br J Cancer. 2003 Feb 24;88(4):516–520.
200. M.Yamamoto, R.Sawaya, S.Mohanam, et al. Expression and localization of urokinase-type plasminogen activator receptor in human gliomas. Cancer Res. 1994 Sep 15;54(18):5016–5020.
201. C.S.Gondi, S.S.Lakka, D.H.Dinh, et al. RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas. Oncogene. 2004 Nov 4;23(52):8486–8496.
202. S.Izumoto, A.Tsuboi, Y.Oka, et al. Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme. J Neurosurg. 2008 May;108(5):963–971.
203. S.Morita, Y.Oka, A.Tsuboi, 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 Apr;36(4):231–236.
204. Y.Nakahara, H.Okamoto, T.Mineta, et al. Expression of the Wilms’ tumor gene product WT1 in glioblastomas and medulloblastomas. Brain Tumor Pathol. 2004;21(3):113–116.
205. R.Shao, R.Francescone, N.Ngernyuang, et al. Anti-YKL-40 antibody and ionizing irradiation synergistically inhibit tumor vascularization and malignancy in glioblastoma. Carcinogenesis. 2014 Feb;35(2):373–382.
206. T.Schumacher, L.Bunse, S.Pusch, et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014 Aug 21;512(7514):324–327.
207. Y.Hou, G.Kohanbash, K.Okada, et al. Novel and shared neoantigen for glioma T cell therapy derived from histone 3 variant H3. 3 K27M mutation. J Immunother Cancer. 2015;3(Suppl 2):P445.
208. F.M.Burnet. Immunological aspects of malignant disease. Lancet. 1967 Jun 3;1(7501):1171–1174.
209. R.W.Baldwin, R.A.Robins. Factors interfering with immunological rejection of tumours. Br Med Bull. 1976 May;32(2):118–123.
210. R.Doll, L.Kinlen. Immunosurveillance and cancer:epidemiological evidence. Br Med J. 1970 Nov 14;4(5732):420–422.
211. D.H.Munn, V.Bronte. Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol. 2016 Apr;39:1–6.
212. Celldex website. Available from: http://ir.celldex.com/releasedetail.cfm?ReleaseID=959021.
213. S.R.Hadrup, A.H.Bakker, C.J.Shu, et al. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat Methods. 2009 Jul;6(7):520–526.
214. N.van Rooij, M.M.van Buuren, D.Philips, et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol. 2013 Nov 10;31(32):e439–e442.
215. B.M.Carreno, V.Magrini, M.Becker-Hapak, et al. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803–808.
216. S.J.Gandhi, A.J.Minn, R.H.Vonderheide, et al. Awakening the immune system with radiation:optimal dose and fractionation. Cancer Lett. 2015 Nov 28;368(2):185–190.
217. C.D.Corso, A.N.Ali, R.Diaz. Radiation-induced tumor neoantigens:imaging and therapeutic implications. Am J Cancer Res. 2011;1(3):390–412.
218. E.B.Golden, D.Frances, I.Pellicciotta, et al. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology. 2014;3:e28518.
219. C.Wild-Bode, M.Weller, A.Rimner, et al. Sublethal irradiation promotes migration and invasiveness of glioma cells:implications for radiotherapy of human glioblastoma. Cancer Res. 2001 Mar 15;61(6):2744–2750.
220. J.Zeng, A.P.See, J.Phallen, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):343–349.
221. I.Tinhofer, F.Niehr, R.Konschak, et al. Next-generation sequencing:hype and hope for development of personalized radiation therapy? Radiat Oncol. 2015;10:183.
222. R.M.Prins, H.Soto, V.Konkankit, et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 2011 Mar 15;17(6):1603–1615.
223. D.A.Mitchell, K.A.Batich, M.D.Gunn, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015 Mar 19;519(7543):366–369.
224. C.S.Cobbs, L.Harkins, M.Samanta, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002 Jun 15;62(12):3347–3350.
225. C.J.Dos Santos, L.M.Stangherlin, E.G.Figueiredo, et al. High prevalence of HCMV and viral load in tumor tissues and peripheral blood of glioblastoma multiforme patients. J Med Virol. 2014 Nov;86(11):1953–1961.
226. S.Libard, S.N.Popova, R.M.Amini, et al. Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade. Plos One. 2014;9(9):e108861.
227. K.G.Lucas, L.Bao, R.Bruggeman, et al. The detection of CMV pp65 and IE1 in glioblastoma multiforme. J Neuro Oncol. 2011 Jun;103(2):231–238.
228. D.A.Mitchell, W.Xie, R.Schmittling, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol. 2008 Feb;10(1):10–18.
229. H.A.Shamran, H.S.Kadhim, A.R.Hussain, et al. Detection of human cytomegalovirus in different histopathological types of glioma in Iraqi patients. Biomed Res Int. 2015;2015:642652.
230. A.Hdeib, A.E.Sloan. Dendritic cell immunotherapy for solid tumors:evaluation of the DCVax(R) platform in the treatment of glioblastoma multiforme. CNS Oncol. 2015;4(2):63–69.• Describes a mechanism of glioma stem cell radioresistance through increased DNA damage checkpoint activation by L1CAM signaling and NBS1 upregulation.
231. Y.Choi, J.Chang. Viral vectors for vaccine applications. Clin Exp Vaccine Res. 2013 Jul;2(2):97–105.
232. Y.Fan, J.J.Moon. Nanoparticle drug delivery systems designed to improve cancer vaccines and immunotherapy. Vaccines. 2015;3(3):662–685.
233. J.E.Boudreau, A.Bonehill, K.Thielemans, et al. Engineering dendritic cells to enhance cancer immunotherapy. Mol Ther. 2011 May;19(5):841–853.
234. D.A.Caruso, L.M.Orme, A.M.Neale, et al. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer. Neuro Oncol. 2004 Jul;6(3):236–246.
235. M.G.Castro, G.J.Baker, P.R.Lowenstein. Blocking immunosuppressive checkpoints for glioma therapy:the more the Merrier! Clin Cancer Res. 2014 Oct 15;20(20):5147–5149.
236. M.K.Hunn, E.Bauer, C.E.Wood, et al. Dendritic cell vaccination combined with temozolomide retreatment:results of a phase I trial in patients with recurrent glioblastoma multiforme. J Neuro Oncol. 2015 Jan;121(2):319–329.
237. B.M.Zussman, J.A.Engh. Outcomes of the ACT III study:rindopepimut (CDX-110) therapy for glioblastoma. Neurosurgery. 2015 Jun;76(6):N17.
238. M.Hsu, S.Sedighim, T.Wang, et al. TCR sequencing can identify and track glioma-infiltrating T cells after DC vaccination. Cancer Immunol Res. 2016 May;4(5):412–418.
239. R.G.Everson, R.M.Jin, X.Wang, et al. Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients. J Immunother Cancer. 2014;2:10.
240. E.Ishikawa, Y.Muragaki, T.Yamamoto, et al. Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma. J Neurosurg. 2014 Sep;121(3):543–553.
241. O.Bloch, C.A.Crane, Y.Fuks, et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma:a phase II, single-arm trial. Neuro Oncol. 2014 Jan;16(2):274–279.
242. T.Kawai, S.Akira. The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors. Nat Immunol. 2010 May;11(5):373–384.
243. L.L.Hartman, J.R.Crawford, M.T.Makale, et al. Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors. J Pediatr Hematol Oncol. 2014 Aug;36(6):451–457.
244. M.R.Rosenfeld, M.C.Chamberlain, S.A.Grossman, et al. A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro Oncol. 2010 Oct;12(10):1071–1077.
245. A.Carpentier, P.Metellus, R.Ursu, et al. Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma:a phase II study. Neuro Oncol. 2010 Apr;12(4):401–408.
246. D.A.Reardon, K.W.Wucherpfennig, G.Freeman, et al. An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma. Expert Rev Vaccines. 2013 Jun;12(6):597–615.
247. V.Chandramohan, D.A.Mitchell, L.A.Johnson, et al. Antibody, T-cell and dendritic cell immunotherapy for malignant brain tumors. Future Oncol. 2013 Jul;9(7):977–990.
248. M.Niyazi, P.N.Harter, E.Hattingen, et al. Bevacizumab and radiotherapy for the treatment of glioblastoma:brothers in arms or unholy alliance? Oncotarget. 2016 Jan 19;7(3):2313–2328.
249. M.Hegde, K.J.Bielamowicz, N.Ahmed. Novel approaches and mechanisms of immunotherapy for glioblastoma. Discov Med. 2014 Mar;17(93):145–154.
250. M.Massimino, V.Biassoni, R.Miceli, et al. Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neuro Oncol. 2014 Jun;118(2):305–312.
251. M.Westphal, O.Heese, J.P.Steinbach, et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer. 2015 Mar;51(4):522–532.
252. M.E.Dudley, J.R.Wunderlich, P.F.Robbins, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850–854.
253. R.A.Morgan, M.E.Dudley, J.R.Wunderlich, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006 Oct 6;314(5796):126–129.
254. A.Schuessler, C.Smith, L.Beagley, et al. Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res. 2014 Jul 1;74(13):3466–3476.
255. H.Ikeda, H.Shiku. Antigen-receptor gene-modified T cells for treatment of glioma. Adv Exp Med Biol. 2012;746:202–215.
256. K.S.Kahlon, C.Brown, L.J.Cooper, et al. Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res. 2004 Dec 15;64(24):9160–9166.
257. C.E.Brown, B.Badie, M.E.Barish, et al. Bioactivity and safety of IL13Ralpha2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015 Sep 15;21(18):4062–4072.
258. N.Ahmed, V.S.Salsman, Y.Kew, et al. HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors. Clin Cancer Res. 2010 Jan 15;16(2):474–485.
259. M.H.Kershaw, J.A.Westwood, P.K.Darcy. Gene-engineered T cells for cancer therapy. Nat Rev Cancer. 2013 08;13(8):525–541. print.
260. L.A.Johnson, J.Scholler, T.Ohkuri, et al. Rational development and characterization of humanized anti–EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med. 2015;7(275):275ra22–75ra22. Epub 2015 Feb 18.
261. D.Castel, C.Philippe, R.Calmon, et al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015;130(6):815–827.
262. T.Siegal. Clinical relevance of prognostic and predictive molecular markers in gliomas. In:J.Schramm, editor. Advances and technical standards in neurosurgery:volume 43. Cham:Springer International Publishing; 2016. p. 91–108.
263. T.Avril, S.Saikali, E.Vauleon, et al. Distinct effects of human glioblastoma immunoregulatory molecules programmed cell death ligand-1 (PDL-1) and indoleamine 2,3-dioxygenase (IDO) on tumour-specific T cell functions. J Neuroimmunol. 2010 Aug 25;225(1–2):22–33.
264. Y.P.Ramirez, J.L.Weatherbee, R.T.Wheelhouse, et al. Glioblastoma multiforme therapy and mechanisms of resistance. Pharmaceuticals. 2013;6(12):1475–1506.
265. R.R.Zhang, K.B.Pointer, J.S.Kuo, et al. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Neurosurgery. 2014 Dec;75(6):N9–10.