Review

Novel Approaches to Pediatric Cancer: Immunotherapy

  • Received: 30 January 2015 Accepted: 17 June 2015 Published: 24 June 2015
  • From the early 20th century, immunotherapy has been studied as a treatment modality for cancers, including in children. Since then, developments in monoclonal antibodies and vaccine therapies have helped to usher in a new era of cancer immunotherapeutics. However, efficacy of these types of therapies has been limited, mostly in part due to low tumor immunogenicity, cancer escape pathways, and toxicities. As researchers investigate the cellular and molecular components of immunotherapies, mechanisms to improve tumor specificity and overcome immune escape have been identified. The goal of immunotherapy now has been to modulate tumor escape pathways while amplifying the immune response by combining innate and adaptive arms of the immune system. Although several limiting factors have been identified, these recent advances in immunotherapy remain at the forefront of pediatric oncologic therapeutic trials. Immunotherapy is now coming to the forefront of precision treatment for a variety of cancers, with evidence that agents targeting immunosuppressive mechanisms for cancer progression can be effective therapy [1-3]. In this review, we review various types of immunotherapy, including the cellular biology, limitations, recent novel therapeutics, and the application of immunotherapy to pediatric oncology.

    Citation: Payal A. Shah, John Goldberg. Novel Approaches to Pediatric Cancer: Immunotherapy[J]. AIMS Medical Science, 2015, 2(2): 104-117. doi: 10.3934/medsci.2015.2.104

    Related Papers:

  • From the early 20th century, immunotherapy has been studied as a treatment modality for cancers, including in children. Since then, developments in monoclonal antibodies and vaccine therapies have helped to usher in a new era of cancer immunotherapeutics. However, efficacy of these types of therapies has been limited, mostly in part due to low tumor immunogenicity, cancer escape pathways, and toxicities. As researchers investigate the cellular and molecular components of immunotherapies, mechanisms to improve tumor specificity and overcome immune escape have been identified. The goal of immunotherapy now has been to modulate tumor escape pathways while amplifying the immune response by combining innate and adaptive arms of the immune system. Although several limiting factors have been identified, these recent advances in immunotherapy remain at the forefront of pediatric oncologic therapeutic trials. Immunotherapy is now coming to the forefront of precision treatment for a variety of cancers, with evidence that agents targeting immunosuppressive mechanisms for cancer progression can be effective therapy [1-3]. In this review, we review various types of immunotherapy, including the cellular biology, limitations, recent novel therapeutics, and the application of immunotherapy to pediatric oncology.


    加载中
    [1] Herbst RS, Soria JC, Kowanetz M, et al. (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515: 563-567. doi: 10.1038/nature14011
    [2] Tumeh PC, Harview CL, Yearley JH, et al. (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515: 568-571. doi: 10.1038/nature13954
    [3] Ansell SM, Lesokhin AM, Borrello I, et al. (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 372: 311-319. doi: 10.1056/NEJMoa1411087
    [4] Coley WB (1907) Sarcoma of the Long Bones: The Diagnosis, Treatment and Prognosis, with a Report of Sixty-Nine Cases. Ann Surg 45: 321-368.
    [5] Topalian SL, Weiner GJ, Pardoll DM (2011) Cancer immunotherapy comes of age. J Clin Oncol 29: 4828-4836. doi: 10.1200/JCO.2011.38.0899
    [6] Grosso JF, Jure-Kunkel MN (2013) CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun 13: 5.
    [7] Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12: 252-264. doi: 10.1038/nrc3239
    [8] de Pasquale MD, Castellano A, de Sio L, et al. (2011) Bevacizumab in pediatric patients: how safe is it? Anticancer Res 31: 3953-3957.
    [9] Okada K, Yamasaki K, Tanaka C, et al. (2013) Phase I study of bevacizumab plus irinotecan in pediatric patients with recurrent/refractory solid tumors. Jpn J Clin Oncol 43: 1073-1079. doi: 10.1093/jjco/hyt124
    [10] Ebb D, Meyers P, Grier H, et al. (2012) Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression: a report from the children's oncology group. J Clin Oncol 30: 2545-2551. doi: 10.1200/JCO.2011.37.4546
    [11] Fry TJ, Lankester AC (2010) Cancer immunotherapy: will expanding knowledge lead to success in pediatric oncology? Hematol Oncol Clin North Am 24: 109-127. doi: 10.1016/j.hoc.2009.11.010
    [12] Dalziel M, Crispin M, Scanlan CN, et al. (2014) Emerging principles for the therapeutic exploitation of glycosylation. Science 343: 1235681. doi: 10.1126/science.1235681
    [13] Kanda Y, Yamada T, Mori K, et al. (2007) Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types. Glycobiology 17: 104-118.
    [14] Morris MJ, Divgi CR, Pandit-Taskar N, et al. (2005) Pilot trial of unlabeled and indium-111-labeled anti-prostate-specific membrane antigen antibody J591 for castrate metastatic prostate cancer. Clin Cancer Res 11: 7454-7461. doi: 10.1158/1078-0432.CCR-05-0826
    [15] Linden O, Hindorf C, Cavallin-Stahl E, et al. (2005) Dose-fractionated radioimmunotherapy in non-Hodgkin's lymphoma using DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab. Clin Cancer Res 11: 5215-5222. doi: 10.1158/1078-0432.CCR-05-0172
    [16] Sharkey RM, Brenner A, Burton J, et al. (2003) Radioimmunotherapy of non-Hodgkin's lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response? J Nucl Med 44: 2000-2018.
    [17] Boerman OC, Koppe MJ, Postema EJ, et al. (2007) Radionuclide therapy of cancer with radiolabeled antibodies. Anticancer Agents Med Chem 7: 335-343. doi: 10.2174/187152007780618126
    [18] Spigel DR, Ervin TJ, Ramlau RA, et al. (2013) Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol 31: 4105-4114. doi: 10.1200/JCO.2012.47.4189
    [19] Kim ES, Neubauer M, Cohn A, et al. (2013) Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. Lancet Oncol 14: 1326-1336. doi: 10.1016/S1470-2045(13)70473-X
    [20] Attias D, Weitzman S (2008) The efficacy of rituximab in high-grade pediatric B-cell lymphoma/leukemia: a review of available evidence. Curr Opin Pediatr 20: 17-22. doi: 10.1097/MOP.0b013e3282f424b0
    [21] Barth MJ, Goldman S, Smith L, et al. (2013) Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukaemia: a Children's Oncology Group report. Br J Haematol 162: 678-683. doi: 10.1111/bjh.12434
    [22] Moreno L, Vaidya SJ, Pinkerton CR, et al. (2013) Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience. Pediatr Blood Cancer 60: 1135-1140. doi: 10.1002/pbc.24452
    [23] Yalcin B, Kremer LC, Caron HN, et al. (2013) High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma. Cochrane Database Syst Rev 8: CD006301.
    [24] Yu AL, Gilman AL, Ozkaynak MF, et al. (2010) Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 363: 1324-1334. doi: 10.1056/NEJMoa0911123
    [25] Ozkaynak MF, Sondel PM, Krailo MD, et al.(2000) Phase I study of chimeric human/murine anti-ganglioside G(D2) monoclonal antibody (ch14.18) with granulocyte-macrophage colony-stimulating factor in children with neuroblastoma immediately after hematopoietic stem-cell transplantation: a Children's Cancer Group Study. J clin oncol 18: 4077-4085.
    [26] Chen X, Soma LA, Fromm JR (2013) Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin. Onco Targets Ther 7: 45-56.
    [27] Brotelle T, Lemal R, Molucon-Chabrot C, et al. (2014) [Gemtuzumab ozogamicin for treatment of acute myeloid leukemia]. Bull Cancer 101: 211-218.
    [28] Daver N, O'Brien S (2013) Novel therapeutic strategies in adult acute lymphoblastic leukemia--a focus on emerging monoclonal antibodies. Curr Hematol Malig Rep 8: 123-131. doi: 10.1007/s11899-013-0160-7
    [29] Kreitman RJ, Pastan I (2011) Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res 17: 6398-6405. doi: 10.1158/1078-0432.CCR-11-0487
    [30] Mussai F, Campana D, Bhojwani D, et al. (2010) Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia. Br J Haematol 150: 352-358. doi: 10.1111/j.1365-2141.2010.08251.x
    [31] Thomas X (2014) Blinatumomab: a new era of treatment for adult ALL? Lancet Oncol 16: 6-7
    [32] Topp MS, Kufer P, Gokbuget N, et al. (2011) Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 29: 2493-2498. doi: 10.1200/JCO.2010.32.7270
    [33] Shah AH, Bregy A, Heros DO, et al. (2013) Dendritic cell vaccine for recurrent high-grade gliomas in pediatric and adult subjects: clinical trial protocol. Neurosurgery 73: 863-867. doi: 10.1227/NEU.0000000000000107
    [34] Ciocca DR, Cayado-Gutierrez N, Maccioni M, et al. (2012) Heat shock proteins (HSPs) based anti-cancer vaccines. Curr Mol Med 12: 1183-1197. doi: 10.2174/156652412803306684
    [35] Yang I, Fang S, Parsa AT (2010) Heat shock proteins in glioblastomas. Neurosurg Clin N Am 21: 111-123. doi: 10.1016/j.nec.2009.09.002
    [36] Graner MW, Bigner DD (2006) Therapeutic aspects of chaperones/heat-shock proteins in neuro-oncology. Expert Rev Anticancer Ther 6: 679-695. doi: 10.1586/14737140.6.5.679
    [37] Hodi FS, O'Day SJ, McDermott DF, et al. (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363: 711-723. doi: 10.1056/NEJMoa1003466
    [38] Kantoff PW, Schuetz TJ, Blumenstein BA, et al. (2010) Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 28: 1099-1105. doi: 10.1200/JCO.2009.25.0597
    [39] Heimberger AB, Sampson JH (2009) The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients. Expert Opin Biol Ther 9: 1087-1098. doi: 10.1517/14712590903124346
    [40] Fest S, Huebener N, Bleeke M, et al. (2009) Survivin minigene DNA vaccination is effective against neuroblastoma. Int J Cancer 125: 104-114. doi: 10.1002/ijc.24291
    [41] Gilboa E (2007) DC-based cancer vaccines. J Clin Invest 117: 1195-1203. doi: 10.1172/JCI31205
    [42] Napolitani G, Rinaldi A, Bertoni F, et al. (2005) Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 6: 769-776. doi: 10.1038/ni1223
    [43] Shen L, Evel-Kabler K, Strube R, et al. (2004) Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity. Nat biotechnol 22: 1546-1553. doi: 10.1038/nbt1035
    [44] Gilboa E (2004) Knocking the SOCS1 off dendritic cells. Nature biotechnology 22: 1521-1522. doi: 10.1038/nbt1204-1521
    [45] Cohen N, Mouly E, Hamdi H, et al. (2006) GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response. Blood 107: 2037-2044. doi: 10.1182/blood-2005-07-2760
    [46] Konkankit VV, Kim W, Koya RC, et al. (2011) Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas ligand pathway. J Transl Med 9: 192. doi: 10.1186/1479-5876-9-192
    [47] Chou J, Voong LN, Mortales CL, et al. (2012) Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer. J Immunother 35: 131-141. doi: 10.1097/CJI.0b013e31824300c7
    [48] Chang CN, Huang YC, Yang DM, et al. (2011) A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J Clin Neurosci 18: 1048-1054. doi: 10.1016/j.jocn.2010.11.034
    [49] Cho DY, Yang WK, Lee HC, et al. (2012) Adjuvant immunotherapy with whole-cell lysate dendritic cells vaccine for glioblastoma multiforme: a phase II clinical trial. World Neurosurg 77: 736-744. doi: 10.1016/j.wneu.2011.08.020
    [50] Liau LM, Prins RM, Kiertscher SM, et al. (2005) 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 11: 5515-5525. doi: 10.1158/1078-0432.CCR-05-0464
    [51] Phuphanich S, Wheeler CJ, Rudnick JD, et al. (2013) Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother 62: 125-135. doi: 10.1007/s00262-012-1319-0
    [52] Wheeler CJ, Black KL, Liu G, et al. (2008) Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res 68: 5955-5964. doi: 10.1158/0008-5472.CAN-07-5973
    [53] Yu JS, Wheeler CJ, Zeltzer PM, et al. (2001) Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res 61: 842-847.
    [54] Dannull J, Haley NR, Archer G, et al. (2013) Melanoma immunotherapy using mature DCs expressing the constitutive proteasome. J Clin Invest 123: 3135-3145.
    [55] Slingluff CL, Jr., Lee S, Zhao F, et al. (2013) A randomized phase II trial of multiepitope vaccination with melanoma peptides for cytotoxic T cells and helper T cells for patients with metastatic melanoma (E1602). Clin Cancer Res 19: 4228-4238. doi: 10.1158/1078-0432.CCR-13-0002
    [56] Dillman R, Barth N, Selvan S, et al. (2004) Phase I/II trial of autologous tumor cell line-derived vaccines for recurrent or metastatic sarcomas. Cancer Biother Radiopharm 19: 581-588. doi: 10.1089/1084978042484812
    [57] Perroud MW, Jr., Honma HN, Barbeiro AS, et al. (2011) Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study. J Exp Clin Cancer Res 30: 65. doi: 10.1186/1756-9966-30-65
    [58] Navada SC, Steinmann J, Lubbert M, et al. (2014) Clinical development of demethylating agents in hematology. J Clin Invest 124: 40-46. doi: 10.1172/JCI69739
    [59] Burdach S, van Kaick B, Laws HJ, et al. (2000) Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Dusseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria. Ann Oncol 11: 1451-1462.
    [60] Wu R, Forget MA, Chacon J, et al. (2012) Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook. Cancer J 18: 160-175. doi: 10.1097/PPO.0b013e31824d4465
    [61] Bridgeman JS, Hawkins RE, Hombach AA, et al. (2010) Building better chimeric antigen receptors for adoptive T cell therapy. Curr Gene Ther 10: 77-90. doi: 10.2174/156652310791111001
    [62] Grupp SA, Prak EL, Boyer J, et al. (2012) Adoptive transfer of autologous T cells improves T-cell repertoire diversity and long-term B-cell function in pediatric patients with neuroblastoma. Clin Cancer Res 18: 6732-6741. doi: 10.1158/1078-0432.CCR-12-1432
    [63] Peres E, Wood GW, Poulik J, et al. (2008) High-dose chemotherapy and adoptive immunotherapy in the treatment of recurrent pediatric brain tumors. Neuropediatrics 39: 151-156. doi: 10.1055/s-0028-1093333
    [64] Bao L, Cowan MJ, Dunham K, et al. (2012) Adoptive immunotherapy with CMV-specific cytotoxic T lymphocytes for stem cell transplant patients with refractory CMV infections. J Immunother 35: 293-298. doi: 10.1097/CJI.0b013e31824300a2
    [65] Park JR, Digiusto DL, Slovak M, et al. (2007) Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther 15: 825-833.
    [66] Ramos CA, Savoldo B, Dotti G (2014) CD19-CAR Trials. Cancer J 20: 112-118. doi: 10.1097/PPO.0000000000000031
    [67] Maude SL, Frey N, Shaw PA, et al. (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371: 1507-1517. doi: 10.1056/NEJMoa1407222
    [68] Tasian SK, Pollard JA, Aplenc R (2014) Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia. Front Oncol 4: 55.
    [69] Hoffman LM, Gore L (2014) Blinatumomab, a Bi-Specific Anti-CD19/CD3 BiTE((R)) Antibody for the Treatment of Acute Lymphoblastic Leukemia: Perspectives and Current Pediatric Applications. Front Oncol 4: 63.
    [70] Hamanishi J, Mandai M, Iwasaki M, et al. (2007) Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A 104: 3360-3365. doi: 10.1073/pnas.0611533104
    [71] Dong H, Zhu G, Tamada K, et al. (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5: 1365-1369. doi: 10.1038/70932
    [72] Toomer KH, Chen Z (2014) Autoimmunity as a Double Agent in Tumor Killing and Cancer Promotion. Front Immunol 5: 116.
    [73] Wolchok JD, Chan TA (2014) Cancer: Antitumour immunity gets a boost. Nature 515: 496-498. doi: 10.1038/515496a
    [74] Parsa AT, Waldron JS, Panner A, et al. (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13: 84-88. doi: 10.1038/nm1517
    [75] Shen JK, Cote GM, Choy E, et al. (2014) Programmed cell death ligand 1 expression in osteosarcoma. Cancer Immunol Res 2: 690-698. doi: 10.1158/2326-6066.CIR-13-0224
    [76] Gilboa E, McNamara J, 2nd, Pastor F (2013) Use of oligonucleotide aptamer ligands to modulate the function of immune receptors. Clin Cancer Res 19: 1054-1062. doi: 10.1158/1078-0432.CCR-12-2067
    [77] Chatterton Z, Burke D, Emslie KR, et al. (2014) Validation of DNA methylation biomarkers for diagnosis of acute lymphoblastic leukemia. Clin Chem 60: 995-1003. doi: 10.1373/clinchem.2013.219956
    [78] Ahsan S, Raabe EH, Haffner MC, et al. (2014) Increased 5-hydroxymethylcytosine and decreased 5-methylcytosine are indicators of global epigenetic dysregulation in diffuse intrinsic pontine glioma. Acta Neuropathol Commun 2: 59. doi: 10.1186/2051-5960-2-59
  • Reader Comments
  • © 2015 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(4417) PDF downloads(1100) Cited by(1)

Article outline

Figures and Tables

Tables(2)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog