Skip to main content
SpringerLink
Log in

Immunotherapy for Neuro-Oncology

  • Chapter
  • First Online:
Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1244))

Abstract

Immunotherapy has changed the landscape of treatment of many solid and hematological malignancies and is at the forefront of cancer breakthroughs. Several circumstances unique to the central nervous system (CNS) such as limited space for an inflammatory response, difficulties with repeated sampling, corticosteroid use for management of cerebral edema, and immunosuppressive mechanisms within the tumor and brain parenchyma have posed challenges in clinical development of immunotherapy for intracranial tumors. Nonetheless, the success of immunotherapy in brain metastases (BMs) from solid cancers such as melanoma and non-small cell lung cancer (NSCLC) proves that the CNS is not an immune-privileged organ and is capable of initiating and regulating immune responses that lead to tumor control. However, the development of immunotherapeutics for the most malignant primary brain tumor, glioblastoma (GBM), has been challenging due to systemic and profound tumor-mediated immunosuppression unique to GBM, intratumoral and intertumoral heterogeneity, low mutation burden, and lack of stably expressed clonal antigens. Here, we review recent advances in the field of immunotherapy for neuro-oncology with a focus on BM and GBM.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Medawar PB. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948;29(1):58–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Woodroofe MN, Bellamy AS, Feldmann M, Davison AN, Cuzner ML. Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis. Possible role for microglia in lesion growth. J Neurol Sci. 1986;74(2–3):135–52.

    Article  CAS  PubMed  Google Scholar 

  3. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Venur VA, Karivedu V, Ahluwalia MS. Systemic therapy for brain metastases. Handb Clin Neurol. 2018;149:137–53.

    Article  PubMed  Google Scholar 

  5. Ostrom QT, Wright CH, Barnholtz-Sloan JS. Brain metastases: epidemiology. Handb Clin Neurol. 2018;149:27–42.

    Article  PubMed  Google Scholar 

  6. Achrol AS, Rennert RC, Anders C, Soffietti R, Ahluwalia MS, Nayak L, et al. Brain metastases. Nat Rev Dis Primers. 2019;5(1):5.

    Article  PubMed  Google Scholar 

  7. Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379(8):722–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.

    Article  CAS  PubMed  Google Scholar 

  10. Hargadon KM, Johnson CE, Williams CJ. Immune checkpoint blockade therapy for cancer: an overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol. 2018;62:29–39.

    Article  CAS  PubMed  Google Scholar 

  11. Callahan MK, Wolchok JD, Allison JP. Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 2010;37(5):473–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 2008;26(4):527–34.

    Article  PubMed  Google Scholar 

  13. Callahan MK, Kluger H, Postow MA, Segal NH, Lesokhin A, Atkins MB, et al. Nivolumab plus ipilimumab in patients with advanced melanoma: updated survival, response, and safety data in a phase I dose-escalation study. J Clin Oncol. 2018;36(4):391–8.

    Article  CAS  PubMed  Google Scholar 

  14. Chukwueke U, Batchelor T, Brastianos P. Management of brain metastases in patients with melanoma. J Oncol Pract. 2016;12(6):536–42.

    Article  PubMed  Google Scholar 

  15. Davies MA, Liu P, McIntyre S, Kim KB, Papadopoulos N, Hwu WJ, et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011;117(8):1687–96.

    Article  PubMed  Google Scholar 

  16. Sloan AE, Nock CJ, Einstein DB. Diagnosis and treatment of mela-noma brain metastasis: a literature review. Cancer Control. 2009;16(3):248–55.

    Article  PubMed  Google Scholar 

  17. Di Giacomo AM, Ascierto PA, Pilla L, Santinami M, Ferrucci PF, Giannarelli D, et al. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol. 2012;13(9):879–86.

    Article  PubMed  CAS  Google Scholar 

  18. Di Giacomo AM, Ascierto PA, Queirolo P, Pilla L, Ridolfi R, Santinami M, et al. Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. Ann Oncol. 2015;26(4):798–803.

    Article  PubMed  Google Scholar 

  19. Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459–65.

    Article  CAS  PubMed  Google Scholar 

  20. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.

    Article  CAS  PubMed  Google Scholar 

  21. Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008;62(4):753–64; discussion 264-6

    Article  PubMed  Google Scholar 

  22. Reardon DA, Gokhale PC, Klein SR, Ligon KL, Rodig SJ, Ramkissoon SH, et al. Glioblastoma eradication following immune checkpoint blockade in an orthotopic, Immunocompetent Model. Cancer Immunol Res. 2016;4(2):124–35.

    Article  CAS  PubMed  Google Scholar 

  23. Fecci PE, Ochiai H, Mitchell DA, Grossi PM, Sweeney AE, Archer GE, 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;13(7):2158–67.

    Article  CAS  PubMed  Google Scholar 

  24. Reardon DA, Omuro A, Brandes AA, Rieger J, Wick A, Sepulveda J, et al. OS10.3 Randomized Phase 3 Study Evaluating the Efficacy and Safety of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: CheckMate 143. Neuro-Oncology. 2017;19(suppl_3):iii21–ii.

    Article  PubMed Central  Google Scholar 

  25. Bristol-Myers Squibb. Bristol-Myers Squibb announces phase 3 checkmate -498 study did not meet primary endpoint of overall survival with opdivo (nivolumab) plus radiation in patients with newly diagnosed MGMT-unmethylated glioblastoma multiforme. 9May 2019. Available from: https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-phase-3-checkmate-498-study-did.

  26. Genoud V, Marinari E, Nikolaev SI, Castle JC, Bukur V, Dietrich PY, et al. Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models. Oncoimmunology. 2018;7(12):e1501137.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yeung JT, Hamilton RL, Ohnishi K, Ikeura M, Potter DM, Nikiforova MN, et al. LOH in the HLA class I region at 6p21 is associated with shorter survival in newly diagnosed adult glioblastoma. Clin Cancer Res. 2013;19(7):1816–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007;13(1):84–8.

    Article  CAS  PubMed  Google Scholar 

  30. Wainwright DA, Chang AL, Dey M, Balyasnikova IV, Kim CK, Tobias A, et al. Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors. Clin Cancer Res. 2014;20(20):5290–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chang N, Ahn SH, Kong DS, Lee HW, Nam DH. The role of STAT3 in glioblastoma progression through dual influences on tumor cells and the immune microenvironment. Mol Cell Endocrinol. 2017;451:53–65.

    Article  CAS  PubMed  Google Scholar 

  32. Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, et al. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell. 2016;164(3):550–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Groot JFD, Penas-Prado M, Mandel JJ, O’Brien BJ, Weathers S-PS, Zhou S, et al. Window-of-opportunity clinical trial of a PD-1 inhibitor in patients with recurrent glioblastoma. J Clin Oncol. 2018;36(15_suppl):2008.

    Article  Google Scholar 

  34. Heimberger AB, Sun W, Hussain SF, Dey M, Crutcher L, Aldape K, et al. Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study. Neuro-Oncology. 2008;10(1):98–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schartner JM, Hagar AR, Van Handel M, Zhang L, Nadkarni N, Badie B. Impaired capacity for upregulation of MHC class II in tumor-associated microglia. Glia. 2005;51(4):279–85.

    Article  PubMed  Google Scholar 

  36. Stevens A, Kloter I, Roggendorf W. Inflammatory infiltrates and natural killer cell presence in human brain tumors. Cancer. 1988;61(4):738–43.

    Article  CAS  PubMed  Google Scholar 

  37. Didenko VV, Ngo HN, Minchew C, Baskin DS. Apoptosis of T lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism. J Neurosurg. 2002;96(3):580–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wischhusen J, Friese MA, Mittelbronn M, Meyermann R, Weller M. HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo. J Neuropathol Exp Neurol. 2005;64(6):523–8.

    Article  CAS  PubMed  Google Scholar 

  39. Wiendl H, Mitsdoerffer M, Hofmeister V, Wischhusen J, Bornemann A, Meyermann R, et al. A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J Immunol. 2002;168(9):4772–80.

    Article  CAS  PubMed  Google Scholar 

  40. Bodmer S, Strommer K, Frei K, Siepl C, de Tribolet N, Heid I, et al. Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. J Immunol. 1989;143(10):3222–9.

    CAS  PubMed  Google Scholar 

  41. Huettner C, Czub S, Kerkau S, Roggendorf W, Tonn JC. Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro. Anticancer Res. 1997;17(5A):3217–24.

    CAS  PubMed  Google Scholar 

  42. Dix AR, Brooks WH, Roszman TL, Morford LA. Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol. 1999;100(1–2):216–32.

    Article  CAS  PubMed  Google Scholar 

  43. Grossman SA, Ye X, Lesser G, Sloan A, Carraway H, Desideri S, et al. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res. 2011;17(16):5473–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018;24(9):1459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gustafson MP, Lin Y, New KC, Bulur PA, O’Neill BP, Gastineau DA, et al. Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone. Neuro-Oncology. 2010;12(7):631–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013;19(12):3165–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol. 2016;34(19):2206–11.

    Article  CAS  PubMed  Google Scholar 

  48. Johanns TM, Miller CA, Dorward IG, Tsien C, Chang E, Perry A, et al. Immunogenomics of hypermutated glioblastoma: a patient with germline POLE deficiency treated with checkpoint blockade immunotherapy. Cancer Discov. 2016;6(11):1230–6.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Viale G, Trapani D, Curigliano G. Mismatch repair deficiency as a predictive biomarker for immunotherapy efficacy. Biomed Res Int. 2017;2017:4719194.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Kamiya-Matsuoka C, Metrus NR, Shaw KR, Penas-Prado M, Weathers S-PS, Loghin ME, et al. The natural course of hypermutator gliomas. J Clin Oncol. 2018;36(15_suppl):2014.

    Article  Google Scholar 

  51. Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology. 2018;20(5):674–86.

    Article  CAS  PubMed  Google Scholar 

  52. Lim M, Omuro A, Vlahovic G, Reardon DA, Sahebjam S, Cloughesy T, et al. 325ONivolumab (nivo) in combination with radiotherapy (RT) ± temozolomide (TMZ): Updated safety results from CheckMate 143 in pts with methylated or unmethylated newly diagnosed glioblastoma (GBM). Ann Oncol. 2017;28(suppl_5):mdx366–mdx.

    Google Scholar 

  53. Reardon DA, Nayak L, Peters KB, Clarke JL, Jordan JT, Groot JFD, et al. Phase II study of pembrolizumab or pembrolizumab plus bevacizumab for recurrent glioblastoma (rGBM) patients. J Clin Oncol. 2018;36(15_suppl):2006.

    Article  Google Scholar 

  54. Amaria RN, Reddy SM, Tawbi HA, Davies MA, Ross MI, Glitza IC, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med. 2018;24(11):1649–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Blank CU, Rozeman EA, Fanchi LF, Sikorska K, van de Wiel B, Kvistborg P, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24(11):1655–61.

    Article  CAS  PubMed  Google Scholar 

  56. Forde PM, Chaft JE, Pardoll DM. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;379(9):e14.

    Article  PubMed  Google Scholar 

  57. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019;25(3):477–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, Lopez-Janeiro A, Porciuncula A, Idoate MA, et al. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat Med. 2019;25(3):470–6.

    Article  CAS  PubMed  Google Scholar 

  59. Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1.

    Article  PubMed  Google Scholar 

  60. Hodges TR, Ott M, Xiu J, Gatalica Z, Swensen J, Zhou S, et al. Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy. Neuro-Oncology. 2017;19(8):1047–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. McGranahan T, Li G, Nagpal S. History and current state of immunotherapy in glioma and brain metastasis. Ther Adv Med Oncol. 2017;9(5):347–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dunn GP, Fecci PE, Curry WT. Cancer immunoediting in malignant glioma. Neurosurgery. 2012;71(2):201–22; discussion 22-3

    Article  PubMed  Google Scholar 

  63. Nduom EK, Weller M, Heimberger AB. Immunosuppressive mechanisms in glioblastoma. Neuro Oncol. 2015;17(Suppl 7):vii9–vii14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wainwright DA, Sengupta S, Han Y, Lesniak MS. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro-Oncology. 2011;13(12):1308–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Lampson LA. Monoclonal antibodies in neuro-oncology: getting past the blood-brain barrier. MAbs. 2011;3(2):153–60.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Gerstner ER, Fine RL. Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J Clin Oncol. 2007;25(16):2306–12.

    Article  PubMed  Google Scholar 

  67. Desai R, Suryadevara CM, Batich KA, Farber SH, Sanchez-Perez L, Sampson JH. Emerging immunotherapies for glioblastoma. Expert Opin Emerg Drugs. 2016;21(2):133–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Heimberger AB, Suki D, Yang D, Shi W, Aldape K. The natural history of EGFR and EGFRvIII in glioblastoma patients. J Transl Med. 2005;3:38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373–85.

    Article  CAS  PubMed  Google Scholar 

  70. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014;512(7514):324–7.

    Article  CAS  PubMed  Google Scholar 

  73. Pellegatta S, Valletta L, Corbetta C, Patane M, Zucca I, Riccardi Sirtori F, et al. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta Neuropathol Commun. 2015;3:4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Platten M, Schilling D, Bunse L, Wick A, Bunse T, Riehl D, Green E, Sanghvi K, Karapanagiotou-Schenkel I, Harting I, Sahm F, Steinbach J, Weyerbrock A, Hense J, Misch M, Krex D, Stevanovic S, Tabatabai G, von Deimling A, Schmitt M, Wick W. ATIM-33. NOA-16: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group evaluating a mutation-specific peptide vaccine targeting idh1r132h in patients with newly diagnosed malignant astrocytomas. Zhang Neuro Oncol. 2018;20(6):vi8–9.

    Google Scholar 

  75. Rampling R, Peoples S, Mulholland PJ, James A, Al-Salihi O, Twelves CJ, et al. A cancer research UK first time in human phase I trial of IMA950 (novel multipeptide therapeutic vaccine) in patients with newly diagnosed glioblastoma. Clin Cancer Res. 2016;22(19):4776–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Migliorini D, Dutoit V, Allard M, Hallez NG, Marinari E, Widmer V, et al. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro-Oncology. 2019;21:923.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234–9.

    Article  CAS  PubMed  Google Scholar 

  78. Baratta MG. Glioblastoma is ‘hot’ for personalized vaccines. Nat Rev Cancer. 2019;19(3):129.

    Article  CAS  PubMed  Google Scholar 

  79. Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanovic S, Gouttefangeas C, et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019;565(7738):240–5.

    Article  CAS  PubMed  Google Scholar 

  80. Graner MW, Bigner DD. Chaperone proteins and brain tumors: potential targets and possible therapeutics. Neuro-Oncology. 2005;7(3):260–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ampie L, Choy W, Lamano JB, Fakurnejad S, Bloch O, Parsa AT. Heat shock protein vaccines against glioblastoma: from bench to bedside. J Neuro-Oncol. 2015;123(3):441–8.

    Article  CAS  Google Scholar 

  82. Bloch O, Crane CA, Fuks Y, Kaur R, Aghi MK, Berger MS, et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro-Oncology. 2014;16(2):274–9.

    Article  CAS  PubMed  Google Scholar 

  83. Liau LM, Black KL, Martin NA, Sykes SN, Bronstein JM, Jouben-Steele L, et al. Treatment of a patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-matched tumor peptides. Case Report Neurosurg Focus. 2000;9(6):e8.

    CAS  PubMed  Google Scholar 

  84. Ardon H, Van Gool SW, Verschuere T, Maes W, Fieuws S, Sciot R, et al. Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother. 2012;61(11):2033–44.

    Article  CAS  PubMed  Google Scholar 

  85. Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS, et al. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018;16(1):142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Jena B, Dotti G, Cooper LJ. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood. 2010;116(7):1035–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Maher J. Clinical immunotherapy of B-cell malignancy using CD19-targeted CAR T-cells. Curr Gene Ther. 2014;14(1):35–43.

    Article  CAS  PubMed  Google Scholar 

  88. Knochelmann HM, Smith AS, Dwyer CJ, Wyatt MM, Mehrotra S, Paulos CM. CAR T cells in solid tumors: blueprints for building effective therapies. Front Immunol. 2018;9:1740.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375(26):2561–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. O’Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Ahmed N, Salsman VS, Kew Y, Shaffer D, Powell S, Zhang YJ, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. John LB, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res. 2013;19(20):5636–46.

    Article  CAS  PubMed  Google Scholar 

  93. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331(6013):44–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Nayyar G, Chu Y, Cairo MS. Overcoming resistance to natural killer cell based immunotherapies for solid tumors. Front Oncol. 2019;9:51.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Ishikawa E, Tsuboi K, Saijo K, Harada H, Takano S, Nose T, et al. Autologous natural killer cell therapy for human recurrent malignant glioma. Anticancer Res. 2004;24(3b):1861–71.

    PubMed  Google Scholar 

  96. Jiang H, McCormick F, Lang FF, Gomez-Manzano C, Fueyo J. Oncolytic adenoviruses as antiglioma agents. Expert Rev Anticancer Ther. 2006;6(5):697–708.

    Article  CAS  PubMed  Google Scholar 

  97. Jiang H, Fueyo J. Healing after death: antitumor immunity induced by oncolytic adenoviral therapy. Oncoimmunology. 2014;3(7):e947872.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Desjardins A, Gromeier M, Herndon JE 2nd, Beaubier N, Bolognesi DP, Friedman AH, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med. 2018;379(2):150–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Perez OD, Logg CR, Hiraoka K, Diago O, Burnett R, Inagaki A, et al. Design and selection of Toca 511 for clinical use: modified retroviral replicating vector with improved stability and gene expression. Mol Ther. 2012;20(9):1689–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Cloughesy TF, Landolfi J, Hogan DJ, Bloomfield S, Carter B, Chen CC, et al. Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. Sci Transl Med. 2016;8(341):341ra75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Lang FF, Conrad C, Gomez-Manzano C, Yung WKA, Sawaya R, Weinberg JS, et al. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J Clin Oncol. 2018;36(14):1419–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Chiocca EA, Nassiri F, Wang J, Peruzzi P, Zadeh G. Viral and other therapies for recurrent glioblastoma: is a 24-month durable response unusual? Neuro-Oncology. 2019;21(1):14–25.

    Article  CAS  PubMed  Google Scholar 

  103. Harrison RA, Anderson MD, Cachia D, Kamiya-Matsuoka C, Weathers SS, O’Brien BJ, et al. Clinical trial participation of patients with glioblastoma at The University of Texas MD Anderson Cancer Center. Eur J Cancer. 2019;112:83–93.

    Article  PubMed  Google Scholar 

  104. Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, 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;17(6):1603–15.

    Article  CAS  PubMed  Google Scholar 

  105. 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.

    Article  CAS  PubMed  Google Scholar 

  106. Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, et al. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial. Br J Cancer. 2003;89(7):1172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Zhai L, Lauing KL, Chang AL, Dey M, Qian J, Cheng Y, et al. The role of IDO in brain tumor immunotherapy. J Neuro-Oncol. 2015;123(3):395–403.

    Article  CAS  Google Scholar 

  108. Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, et al. T cell apoptosis by tryptophan catabolism. Cell Death Differ. 2002;9(10):1069–77.

    Article  CAS  PubMed  Google Scholar 

  109. Bogdahn U, Hau P, Stockhammer G, Venkataramana NK, Mahapatra AK, Suri A, et al. Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro-Oncology. 2011;13(1):132–42.

    Article  CAS  PubMed  Google Scholar 

  110. den Hollander MW, Bensch F, AWJM G, Enting RH, Bunskoek S, THO M, et al. 89zr-GC1008 PET imaging and GC1008 treatment of recurrent glioma patients. J Clin Oncol. 2013;31(15_suppl):2050.

    Article  Google Scholar 

  111. Rodon J, Carducci MA, Sepulveda-Sanchez JM, Azaro A, Calvo E, Seoane J, et al. First-in-human dose study of the novel transforming growth factor-beta receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. Clin Cancer Res. 2015;21(3):553–60.

    Article  CAS  PubMed  Google Scholar 

  112. Roy LO, Poirier MB, Fortin D. Differential expression and clinical significance of transforming growth factor-beta isoforms in GBM tumors. Int J Mol Sci. 2018;19(4):1113.

    Article  PubMed Central  CAS  Google Scholar 

  113. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013;19(10):1264–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Butowski N, Colman H, De Groot JF, Omuro AM, Nayak L, Wen PY, et al. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study. Neuro-Oncology. 2016;18(4):557–64.

    Article  PubMed  Google Scholar 

  115. Goldberg MV, Drake CG. LAG-3 in cancer immunotherapy. Curr Top Microbiol Immunol. 2011;344:269–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Harris-Bookman S, Mathios D, Martin AM, Xia Y, Kim E, Xu H, et al. Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma. Int J Cancer. 2018;143(12):3201–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Pollok KE, Kim YJ, Zhou Z, Hurtado J, Kim KK, Pickard RT, et al. Inducible T cell antigen 4-1BB. Analysis of expression and function. J Immunol. 1993;150(3):771–81.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuro-Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Nazanin Majd & John de Groot

  2. Department of Neurology, University of Texas Austin Dell Medical School, Austin, TX, USA

    Pushan Dasgupta

Authors
  1. Nazanin Majd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pushan Dasgupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John de Groot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John de Groot .

Editor information

Editors and Affiliations

  1. MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Aung Naing

  2. Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Joud Hajjar

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Majd, N., Dasgupta, P., de Groot, J. (2020). Immunotherapy for Neuro-Oncology. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 1244. Springer, Cham. https://doi.org/10.1007/978-3-030-41008-7_8

Download citation

Publish with us

Policies and ethics

Search

Navigation