Cellular and vaccine therapeutic approaches for gliomas

Michelle J Hickey, Colin C Malone, Kate L Erickson, Martin R Jadus, Robert M Prins, Linda M Liau, Carol A Kruse, Michelle J Hickey, Colin C Malone, Kate L Erickson, Martin R Jadus, Robert M Prins, Linda M Liau, Carol A Kruse

Abstract

Despite new additions to the standard of care therapy for high grade primary malignant brain tumors, the prognosis for patients with this disease is still poor. A small contingent of clinical researchers are focusing their efforts on testing the safety, feasibility and efficacy of experimental active and passive immunotherapy approaches for gliomas and are primarily conducting Phase I and II clinical trials. Few trials have advanced to the Phase III arena. Here we provide an overview of the cellular therapies and vaccine trials currently open for patient accrual obtained from a search of http://www.clinicaltrials.gov. The search was refined with terms that would identify the Phase I, II and III immunotherapy trials open for adult glioma patient accrual in the United States. From the list, those that are currently open for patient accrual are discussed in this review. A variety of adoptive immunotherapy trials using ex vivo activated effector cell preparations, cell-based and non-cell-based vaccines, and several combination passive and active immunotherapy approaches are discussed.

Figures

Figure 1
Figure 1
Map of the United States showing geographical locations of immunotherapy clinical trials discussed in the review. States shaded in gray have immune therapy clinical trials that are open and currently accruing patients. The city locations of one or more cellular therapy trials are indicated with a blue star, the vaccine therapy trials with a red circle, and the combined cellular and vaccine therapy trials with a white triangle.

References

    1. CBTRUS. CBTRUS Statistical report: Primary brain and central nervous system tumors diagnosed in the United States, 2004-2006. Central Brain Tumor Registry of the United States; 2010.
    1. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O'Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110. doi: 10.1016/j.ccr.2009.12.020.
    1. Huse JT, Holland EC. Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 2010;10:319–31. doi: 10.1038/nrc2818.
    1. .
    1. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66. doi: 10.1016/S1470-2045(09)70025-7.
    1. Paul D, Kruse C. Immunologic Approaches to Therapy for Brain Tumors. Current Neurol Neurosci Reports. 2001;1:238–44. doi: 10.1007/s11910-001-0024-8.
    1. Virasch N, Kruse CA. Strategies using the immune system for therapy of brain tumors. Hematol Oncol Clin North Am. 2001;15:1053–71. doi: 10.1016/S0889-8588(05)70267-7.
    1. Zhang JG, Eguchi J, Kruse CA, Gomez GG, Fakhrai H, Schroter S, Ma W, Hoa N, Minev B, Delgado C, Wepsic HT, Okada H, Jadus MR. Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Clin Cancer Res. 2007;13:566–75. doi: 10.1158/1078-0432.CCR-06-1576.
    1. 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;64:9160–6. doi: 10.1158/0008-5472.CAN-04-0454.
    1. Yaghoubi SS, Jensen MC, Satyamurthy N, Budhiraja S, Paik D, Czernin J, Gambhir SS. Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol. 2009;6:53–8. doi: 10.1038/ncponc1278.
    1. Debinski W. Recombinant cytotoxins specific for cancer cells. Ann N Y Acad Sci. 1999;886:297–9. doi: 10.1111/j.1749-6632.1999.tb09441.x.
    1. Mintz A, Gibo DM, Slagle-Webb B, Christensen ND, Debinski W. IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13. Neoplasia. 2002;4:388–99. doi: 10.1038/sj.neo.7900234.
    1. Barth S. hIL-13-PE38QQR. NeoPharm. Curr Opin Investig Drugs. 2001;2:1309–13.
    1. Debinski W, Obiri NI, Powers SK, Pastan I, Puri RK. Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin. Clin Cancer Res. 1995;1:1253–8.
    1. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, Nabors LB, Cobbs CG, Britt WJ. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62:3347–50.
    1. Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, Sampson JH. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neurooncol. 2008;10:10–8.
    1. Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol. 2008;116:79–86. doi: 10.1007/s00401-008-0359-1.
    1. Ahmed N, Salsman VS, Kew Y, Shaffer D, Powell S, Zhang YJ, Grossman RG, Heslop HE, Gottschalk S. HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors. Clin Cancer Res. 2010;16:474–85. doi: 10.1158/1078-0432.CCR-09-1322.
    1. Zhang JG, Kruse CA, Driggers L, Hoa N, Wisoff J, Allen JC, Zagzag D, Newcomb EW, Jadus MR. Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy. J Neurooncol. 2008;88:65–76. doi: 10.1007/s11060-008-9534-4.
    1. Bao L, Sun Q, Lucas KG. Rapid generation of CMV pp65-specific T cells for immunotherapy. J Immunother. 2007;30:557–61. doi: 10.1097/CJI.0b013e31803b945b.
    1. Kruse CA, Rubinstein D. In: Brain Tumor Immunotherapy. Liau LM, Cloughesy TF, Becker DP, Bigner DD, editor. Totowa: Humana Press; 2001. Cytotoxic T Lymphocytes Reactive to Patient Major Histocompatibility Proteins for Therapy of Recurrent Primary Brain Tumors; pp. 149–70.
    1. Dillman RO, Duma CM, Ellis RA, Cornforth AN, Schiltz PM, Sharp SL, DePriest MC. Intralesional lymphokine-activated killer cells as adjuvant therapy for primary glioblastoma. J Immunother. 2009;32:914–9. doi: 10.1097/CJI.0b013e3181b2910f.
    1. Walker DG, Laherty R, Tomlinson FH, Chuah T, Schmidt C. Results of a phase I dendritic cell vaccine trial for malignant astrocytoma: potential interaction with adjuvant chemotherapy. J Clin Neurosci. 2008;15:114–21. doi: 10.1016/j.jocn.2007.08.007.
    1. Wheeler CJ, Das A, Liu G, Yu JS, Black KL. Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res. 2004;10:5316–26. doi: 10.1158/1078-0432.CCR-04-0497.
    1. Insug O, Ku G, Ertl HC, Blaszczyk-Thurin M. A dendritic cell vaccine induces protective immunity to intracranial growth of glioma. Anticancer Res. 2002;22:613–21.
    1. Kobayashi T, Yamanaka R, Homma J, Tsuchiya N, Yajima N, Yoshida S, Tanaka R. Tumor mRNA-loaded dendritic cells elicit tumor-specific CD8(+) cytotoxic T cells in patients with malignant glioma. Cancer Immunol Immunother. 2003;52:632–7. doi: 10.1007/s00262-003-0408-5.
    1. Smith BD, Kasamon YL, Kowalski J, Gocke C, Murphy K, Miller CB, Garrett-Mayer E, Tsai HL, Qin L, Chia C, Biedrzycki B, Harding TC, Tu GH, Jones R, Hege K, Levitsky HI. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res. 2010;16:338–47. doi: 10.1158/1078-0432.CCR-09-2046.
    1. Moriai R, Asanuma K, Kobayashi D, Yajima T, Yagihashi A, Yamada M, Watanabe N. Quantitative analysis of the anti-apoptotic gene survivin expression in malignant haematopoietic cells. Anticancer Res. 2001;21:595–600.
    1. Buhring HJ, Sures I, Jallal B, Weiss FU, Busch FW, Ludwig WD, Handgretinger R, Waller HD, Ullrich A. The receptor tyrosine kinase p185HER2 is expressed on a subset of B-lymphoid blasts from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia. Blood. 1995;86:1916–23.
    1. Schmitt M, Li L, Giannopoulos K, Chen J, Brunner C, Barth T, Schmitt A, Wiesneth M, Dohner K, Dohner H, Greiner J. Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules. Exp Hematol. 2006;34:1709–19. doi: 10.1016/j.exphem.2006.07.009.
    1. Greiner J, Ringhoffer M, Simikopinko O, Szmaragowska A, Huebsch S, Maurer U, Bergmann L, Schmitt M. Simultaneous expression of different immunogenic antigens in acute myeloid leukemia. Exp Hematol. 2000;28:1413–22. doi: 10.1016/S0301-472X(00)00550-6.
    1. 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;57:4130–40.
    1. Heimberger AB, Sampson JH. The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients. Expert Opin Biol Ther. 2009;9:1087–98. doi: 10.1517/14712590903124346.
    1. Aucouturier J, Dupuis L, Deville S, Ascarateil S, Ganne V. Montanide ISA 720 and 51: a new generation of water in oil emulsions as adjuvants for human vaccines. Expert Rev Vaccines. 2002;1:111–8. doi: 10.1586/14760584.1.1.111.
    1. Graner MW, Cumming RI, Bigner DD. The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences. J Neurosci. 2007;27:11214–27. doi: 10.1523/JNEUROSCI.3588-07.2007.
    1. Hermisson M, Strik H, Rieger J, Dichgans J, Meyermann R, Weller M. Expression and functional activity of heat shock proteins in human glioblastoma multiforme. Neurology. 2000;54:1357–65.
    1. Blachere NE, Li Z, Chandawarkar RY, Suto R, Jaikaria NS, Basu S, Udono H, Srivastava PK. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med. 1997;186:1315–22. doi: 10.1084/jem.186.8.1315.
    1. Przepiorka D, Srivastava PK. Heat shock protein--peptide complexes as immunotherapy for human cancer. Mol Med Today. 1998;4:478–84. doi: 10.1016/S1357-4310(98)01345-8.
    1. 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;48:113–20. doi: 10.1023/A:1006456421177.
    1. Plautz GE, Barnett GH, Miller DW, Cohen BH, Prayson RA, Krauss JC, Luciano M, Kangisser DB, Shu S. Systemic T cell adoptive immunotherapy of malignant gliomas. J Neurosurg. 1998;89:42–51. doi: 10.3171/jns.1998.89.1.0042.
    1. Plautz GE, Miller DW, Barnett GH, Stevens GH, Maffett S, Kim J, Cohen PA, Shu S. T cell adoptive immunotherapy of newly diagnosed gliomas. Clin Cancer Res. 2000;6:2209–18.
    1. Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, Baynes R, Wood G. 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:e9. doi: 10.3171/foc.2000.9.6.10.
    1. Kruse CA, Cepeda L, Owens B, Johnson SD, Stears J, Lillehei KO. Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2. Cancer Immunol Immunother. 1997;45:77–87. doi: 10.1007/s002620050405.
    1. 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;64:4973–9. doi: 10.1158/0008-5472.CAN-03-3505.
    1. Quattrocchi KB, Miller CH, Cush S, Bernard SA, Dull ST, Smith M, Gudeman S, Varia MA. Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neurooncol. 1999;45:141–57. doi: 10.1023/A:1006293606710.
    1. Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF, Roth MD. 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;11:5515–25. doi: 10.1158/1078-0432.CCR-05-0464.
    1. Wheeler C, Black K, Liu G, Mazer M, Zhang X, Pepkowitz S, Goldfinger D, Ng H, Irwin D, Yu J. Vaccination Elicits Correlated Immune and Clinical Responses in Glioblastoma Multiforme Patients. Cancer Res. 2008;68:5955–64. doi: 10.1158/0008-5472.CAN-07-5973.
    1. Wheeler CJ, Black KL, Liu G, Ying H, Yu JS, Zhang W, Lee PK. Thymic CD8+ T cell production strongly influences tumor antigen recognition and age-dependent glioma mortality. J Immunol. 2003;171:4927–33.
    1. Rutkowski S, De Vleeschouwer S, Kaempgen E, Wolff JE, Kuhl J, Demaerel P, Warmuth-Metz M, Flamen P, Van Calenbergh F, Plets C, Sorensen N, Opitz A, Van Gool SW. Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study. Br J Cancer. 2004;91:1656–62.
    1. De Vleeschouwer S, Van Calenbergh F, Demaerel P, Flamen P, Rutkowski S, Kaempgen E, Wolff JE, Plets C, Sciot R, Van Gool SW. Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy. Case report. J Neurosurg. 2004;100:492–7.
    1. De Vleeschouwer S, Fieuws S, Rutkowski S, Van Calenbergh F, Van Loon J, Goffin J, Sciot R, Wilms G, Demaerel P, Warmuth-Metz M, Soerensen N, Wolff JE, Wagner S, Kaempgen E, Van Gool SW. Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin Cancer Res. 2008;14:3098–104. doi: 10.1158/1078-0432.CCR-07-4875.
    1. Van Meter ME, Kim ES. Bevacizumab: current updates in treatment. Curr Opin Oncol. 2010. in press .
    1. Agha CA, Ibrahim S, Hassan A, Elias DA, Fathallah-Shaykh HM. Bevacizumab is active as a single agent against recurrent malignant gliomas. Anticancer Res. 2010;30:609–11.
    1. Bergsneider M, Sehati N, Villablanca P, McArthur DL, Becker DP, Liau LM. Mahaley Clinical Research Award: Extent of glioma resection using low-field (0.2 T) versus high-field (1.5 T) intraoperative MRI and image-guided frameless neuronavigation. Clin Neurosurg. 2005;52:389–99.
    1. Study of a Drug [DCVax®-Brain] to Treat Newly Diagnosed GBM Brain Cancer.
    1. DCVax® - Brain Phase II Clinical Trial.
    1. Precision Targeted Immunotherapies.
    1. Li GMS, Wong AJ. The epidermal growth factor variant III peptide vaccine for treatment of malignant gliomas. Neurosurg Clin N Am. 2010;21:87–93. doi: 10.1016/j.nec.2009.08.004.
    1. Interim Positive Results From Phase 2b Brain Cancer Study With Rindopepimut (PF-04948568 or CDX-110) Presented at 46th Annual ASCO Meeting.
    1. ImmunoCellular Theraputics, Ltd.
    1. ImmunoCellular Therapeutics Signs Agreement With Averion International To Conduct Phase II Glioblastoma Study.
    1. Antigenics.
    1. Jian B, Yang I, Parsa AT. Monitoring immune responses after glioma vaccine immunotherapy. Neurosurg Clin N Am. 2010;21:195–9. doi: 10.1016/j.nec.2009.09.004.
    1. Dang Y, Disis ML. Identification of immunologic biomarkers associated with clinical response after immune-based therapy for cancer. Ann N Y Acad Sci. 2009;1174:81–7. doi: 10.1111/j.1749-6632.2009.04937.x.
    1. Walker EB, Disis ML. Monitoring immune responses in cancer patients receiving tumor vaccines. Int Rev Immunol. 2003;22:283–319. doi: 10.1080/08830180305226.
    1. Sasaki K, Zhu X, Vasquez C, Nishimura F, Dusak JE, Huang J, Fujita M, Wesa A, Potter DM, Walker PR, Storkus WJ, Okada H. Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumors. Cancer Res. 2007;67:6451–8. doi: 10.1158/0008-5472.CAN-06-3280.
    1. Rizzuto GA, Merghoub T, Hirschhorn-Cymerman D, Liu C, Lesokhin AM, Sahawneh D, Zhong H, Panageas KS, Perales MA, Altan-Bonnet G, Wolchok JD, Houghton AN. Self-antigen-specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response. J Exp Med. 2009;206:849–66. doi: 10.1084/jem.20081382.
    1. Gomez GG, Kruse CA. Mechanisms of malignant glioma immune resistance and sources of immunosuppression. Gene Ther Mol Biol. 2006;10:133–46.
    1. Khan-Farooqi HR, Prins RM, Liau LM. Tumor immunology, immunomics and targeted immunotherapy for central nervous system malignancies. Neurol Res. 2005;27:692–702. doi: 10.1179/016164105X49490.
    1. Prins RM, Liau LM. Immunology and immunotherapy in neurosurgical disease. Neurosurgery. 2003;53:144–52. doi: 10.1227/01.NEU.0000068865.34216.3A.
    1. Wang W, Tai CK, Kershaw AD, Solly SK, Klatzmann D, Kasahara N, Chen TC. Use of replication-competent retroviral vectors in an immunocompetent intracranial glioma model. Neurosurg Focus. 2006;20:E25. doi: 10.3171/foc.2006.20.4.1.
    1. Tai CK, Logg CR, Park JM, Anderson WF, Press MF, Kasahara N. Antibody-mediated targeting of replication-competent retroviral vectors. Hum Gene Ther. 2003;14:789–802. doi: 10.1089/104303403765255174.
    1. Reporter.
    1. Yang IHN, Smith ZA, Han SJ, Parsa AT. Distinguishing glioma recurrence from treatment effect after radiochemotherapy and immunotherapy. Neurosurg Clin N Am. 2010;21:181–6. doi: 10.1016/j.nec.2009.08.003.
    1. Floeth FW, Wittsack HJ, Engelbrecht V, Weber F. Comparative follow-up of enhancement phenomena with MRI and Proton MR Spectroscopic Imaging after intralesional immunotherapy in glioblastoma--Report of two exceptional cases. Zentralbl Neurochir. 2002;63:23–8. doi: 10.1055/s-2002-31579.
    1. Dendreon.
    1. Higano CS, Small EJ, Schellhammer P, Yasothan U, Gubernick S, Kirkpatrick P, Kantoff PW. Sipuleucel-T. Nat Rev Drug Discov. 2010;9:513–4. doi: 10.1038/nrd3220.
    1. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22. doi: 10.1056/NEJMoa1001294.

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