Home LiteratureArticle Details
PMID: 22748269 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Immunotherapies for non-small-cell lung cancer and mesothelioma.

The Lancet. Oncology ·Vol. 13 ·No. 7 ·2012-07-00 ·Pages e301-10

Thomas A, Hassan R

Abstract

Non-small-cell lung cancer and mesothelioma are thoracic malignancies, which in their advanced stages are incurable and have poor prognosis. Advances in our understanding of immune responses to tumours, tumour immunosuppression mechanisms, and tumour-specific shared antigens enabled successful early clinical trials of several specific and non-specific immunotherapies. For non-small-cell lung cancer, phase 3 clinical trial results of Toll-like receptor agonists show little promise. However, ongoing phase 3 trials are assessing melanoma-associated antigen A3 vaccine, liposomal BLP25, belagenpumatucel-L, and talactoferrin. In mesothelioma, immunotherapies being investigated include dendritic cell-based and Listeria-based vaccines, and allogeneic tumour cell and WT1 analogue peptide vaccines. Selection of appropriate patients and disease stages for immunotherapy, measurement of tumour-specific immune responses, and understanding the association between immune and clinical responses are some of the major challenges for the development of immunotherapies for these malignancies.

MeSH Terms
Antigens, Neoplasm/immunology CTLA-4 Antigen/antagonists & inhibitors Carcinoma, Non-Small-Cell Lung/therapy Dendritic Cells/immunology GPI-Linked Proteins/immunology Humans Immunotherapy/methods Lung Neoplasms/therapy Mesothelin Mesothelioma/therapy Neoplasm Proteins/immunology Toll-Like Receptors/agonists WT1 Proteins/immunology
Chemicals
Antigens, Neoplasm CTLA-4 Antigen GPI-Linked Proteins MAGEA3 protein, human Neoplasm Proteins Toll-Like Receptors WT1 Proteins Mesothelin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Thomas Anish
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hassan Raffit
References (85)
85 references, click to expand
  1. Advances in malignant mesothelioma.
    N Engl J Med. 2005 Oct 13;353(15):1591-603 PMID: 16221782
  2. Toll-like receptor 9 agonists as cancer therapeutics.
    Expert Opin Investig Drugs. 2011 Mar;20(3):361-72 PMID: 21254877
  3. Phase I trial of oral talactoferrin alfa in refractory solid tumors.
    Invest New Drugs. 2006 May;24(3):233-40 PMID: 16193240
  4. WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer.
    Cancer Immunol Immunother. 2010 Oct;59(10):1467-79 PMID: 20532500
  5. Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism.
    Cancer Res. 2003 Feb 1;63(3):642-6 PMID: 12566308
  6. Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients.
    Clin Cancer Res. 2005 May 15;11(10):3814-20 PMID: 15897581
  7. Cancer/testis (CT) antigens: potential targets for immunotherapy.
    Cancer Sci. 2009 Nov;100(11):2014-21 PMID: 19719775
  8. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
    J Clin Oncol. 2010 Jul 1;28(19):3167-75 PMID: 20516446
  9. Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy.
    Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2909-14 PMID: 8610141
  10. Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma.
    Cancer Biol Ther. 2005 Mar;4(3):342-6 PMID: 15846066
  11. Listeria-based cancer vaccines that segregate immunogenicity from toxicity.
    Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13832-7 PMID: 15365184
  12. Improved endpoints for cancer immunotherapy trials.
    J Natl Cancer Inst. 2010 Sep 22;102(18):1388-97 PMID: 20826737
  13. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours.
    J Thorac Oncol. 2007 Aug;2(8):706-14 PMID: 17762336
  14. Constitutive secretion of bioactive transforming growth factor beta 1 by small cell lung cancer cell lines.
    Eur J Cancer. 1994;30A(14):2125-9 PMID: 7857713
  15. Cancer immunotherapy: moving beyond current vaccines.
    Nat Med. 2004 Sep;10(9):909-15 PMID: 15340416
  16. Vaccination with BLP25 liposome vaccine to treat non-small cell lung and prostate cancers.
    Expert Rev Vaccines. 2005 Jun;4(3):249-57 PMID: 16026241
  17. TGFbeta signalling: a complex web in cancer progression.
    Nat Rev Cancer. 2010 Jun;10(6):415-24 PMID: 20495575
  18. A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma.
    Br J Cancer. 2000 Oct;83(7):853-7 PMID: 10970684
  19. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer.
    J Clin Oncol. 2006 Oct 10;24(29):4721-30 PMID: 16966690
  20. Sera from patients with malignant mesothelioma can contain autoantibodies.
    Lung Cancer. 1998 Jun;20(3):175-84 PMID: 9733052
  21. SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results.
    Ann Oncol. 2004 Jun;15(6):906-14 PMID: 15151947
  22. Randomized phase II trial of a toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage non-small-cell lung cancer.
    J Clin Oncol. 2008 Aug 20;26(24):3979-86 PMID: 18711188
  23. Therapeutic potential of Toll-like receptor 9 activation.
    Nat Rev Drug Discov. 2006 Jun;5(6):471-84 PMID: 16763660
  24. Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells.
    FASEB J. 2008 Aug;22(8):2747-57 PMID: 18364398
  25. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation.
    J Immunol. 2002 May 1;168(9):4272-6 PMID: 11970966
  26. Mesothelioma environment comprises cytokines and T-regulatory cells that suppress immune responses.
    Eur Respir J. 2006 Jun;27(6):1086-95 PMID: 16540497
  27. Plasma transforming growth factor-beta1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma.
    Cancer. 1999 Nov 1;86(9):1712-9 PMID: 10547543
  28. Cancer vaccines: moving beyond current paradigms.
    Clin Cancer Res. 2007 Jul 1;13(13):3776-82 PMID: 17606707
  29. Characterization of preexisting MAGE-A3-specific CD4+ T cells in cancer patients and healthy individuals and their activation by protein vaccination.
    J Immunol. 2009 Oct 1;183(7):4800-8 PMID: 19734225
  30. Human MUC1 carcinoma-associated protein confers resistance to genotoxic anticancer agents.
    Cancer Cell. 2004 Feb;5(2):163-75 PMID: 14998492
  31. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma.
    Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90 PMID: 20167848
  32. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer.
    J Clin Oncol. 2011 Jul 1;29(19):2667-74 PMID: 21632509
  33. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
    N Engl J Med. 2002 Jan 10;346(2):92-8 PMID: 11784875
  34. Mesothelin: a new target for immunotherapy.
    Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3937-42 PMID: 15217923
  35. A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer.
    J Thorac Oncol. 2011 Jun;6(6):1098-103 PMID: 21532506
  36. The use of mycobacterial adjuvant-based agents for immunotherapy of cancer.
    Vaccine. 2008 Sep 15;26(39):4984-90 PMID: 18625281
  37. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
    J Clin Oncol. 2003 Jul 15;21(14):2636-44 PMID: 12860938
  38. Immunogenicity and antitumor activity of a liposomal MUC1 peptide-based vaccine.
    Int J Cancer. 1998 Jan 19;75(2):295-302 PMID: 9462722
  39. Localised spontaneous regression in mesothelioma -- possible immunological mechanism.
    Lung Cancer. 2001 May;32(2):197-201 PMID: 11325491
  40. L-BLP25: a peptide vaccine strategy in non small cell lung cancer.
    Clin Cancer Res. 2007 Aug 1;13(15 Pt 2):s4652-4 PMID: 17671159
  41. Therapeutic cancer vaccines: are we there yet?
    Immunol Rev. 2011 Jan;239(1):27-44 PMID: 21198663
  42. Wilms' tumour gene 1 (WT1) in human neoplasia.
    Leukemia. 2005 Aug;19(8):1318-23 PMID: 15920488
  43. MUC1 mediates transendothelial migration in vitro by ligating endothelial cell ICAM-1.
    Clin Exp Metastasis. 2005;22(6):475-83 PMID: 16320110
  44. Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44.
    J Biol Chem. 2001 Jun 15;276(24):20809-12 PMID: 11320076
  45. Dendritic cells as therapeutic vaccines against cancer.
    Nat Rev Immunol. 2005 Apr;5(4):296-306 PMID: 15803149
  46. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.
    J Clin Oncol. 2005 Sep 20;23(27):6674-81 PMID: 16170175
  47. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.
    Clin Cancer Res. 2005 Nov 15;11(22):8055-62 PMID: 16299236
  48. Human MUC1 carcinoma antigen regulates intracellular oxidant levels and the apoptotic response to oxidative stress.
    J Biol Chem. 2003 Sep 12;278(37):35458-64 PMID: 12826677
  49. Randomized, double-blind, placebo-controlled phase II study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy.
    J Clin Oncol. 2011 Nov 1;29(31):4129-36 PMID: 21969509
  50. Tissue microarray evaluation of Melanoma antigen E (MAGE) tumor-associated antigen expression: potential indications for specific immunotherapy and prognostic relevance in squamous cell lung carcinoma.
    Ann Surg. 2002 Dec;236(6):785-93; discussion 793 PMID: 12454517
  51. Paclitaxel reduces regulatory T cell numbers and inhibitory function and enhances the anti-tumor effects of the TLR9 agonist PF-3512676 in the mouse.
    Cancer Immunol Immunother. 2009 Apr;58(4):615-28 PMID: 18802696
  52. Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung cancer.
    Clin Lung Cancer. 2001 Aug;3(1):49-57; discussion 58 PMID: 14656392
  53. Changing trends in US mesothelioma incidence.
    Occup Environ Med. 2004 May;61(5):438-41 PMID: 15090665
  54. Generation of dendritic cell-based vaccines for cancer therapy.
    Br J Cancer. 2002 May 20;86(10):1529-33 PMID: 12085199
  55. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction.
    Clin Cancer Res. 2012 Feb 1;18(3):858-68 PMID: 22147941
  56. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial.
    J Cancer Res Clin Oncol. 2011 Sep;137(9):1337-42 PMID: 21744082
  57. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria.
    Clin Cancer Res. 2009 Dec 1;15(23):7412-20 PMID: 19934295
  58. Human DF3/MUC1 carcinoma-associated protein functions as an oncogene.
    Oncogene. 2003 Sep 4;22(38):6107-10 PMID: 12955090
  59. Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients.
    Cancer Gene Ther. 2009 Aug;16(8):620-4 PMID: 19287371
  60. Cancer statistics, 2010.
    CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300 PMID: 20610543
  61. Lymphocytic infiltration of pleural mesothelioma and its significance for survival.
    S Afr Med J. 1982 Jun 26;61(26):1007-9 PMID: 7089768
  62. Human lung cancer cells express functionally active Toll-like receptor 9.
    Respir Res. 2005 Jan 04;6:1 PMID: 15631627
  63. T-cell regulation by CD28 and CTLA-4.
    Nat Rev Immunol. 2001 Dec;1(3):220-8 PMID: 11905831
  64. Safety of BLP25 liposome vaccine (L-BLP25) in Japanese patients with unresectable stage III NSCLC after primary chemoradiotherapy: preliminary results from a Phase I/II study.
    Jpn J Clin Oncol. 2011 May;41(5):718-22 PMID: 21393255
  65. Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo.
    Cancer Res. 1997 Aug 1;57(15):3200-7 PMID: 9242450
  66. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer.
    Ann Oncol. 2012 Jan;23(1):72-77 PMID: 21464154
  67. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells.
    Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77 PMID: 15764728
  68. Characterization of effusion-infiltrating T cells: benign versus malignant effusions.
    Clin Cancer Res. 2004 Apr 15;10(8):2600-8 PMID: 15102661
  69. Toll-like receptor signalling.
    Nat Rev Immunol. 2004 Jul;4(7):499-511 PMID: 15229469
  70. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
    N Engl J Med. 2011 Jun 30;364(26):2517-26 PMID: 21639810
  71. Peptide epitopes from the Wilms' tumor 1 oncoprotein stimulate CD4+ and CD8+ T cells that recognize and kill human malignant mesothelioma tumor cells.
    Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4547-55 PMID: 17671141
  72. Spontaneous remission of a non-small cell lung cancer possibly caused by anti-NY-ESO-1 immunity.
    Lung Cancer. 2009 Jul;65(1):119-22 PMID: 19193472
  73. Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
    N Engl J Med. 2010 Jul 29;363(5):411-22 PMID: 20818862
  74. A multicenter open-label study to assess the safety of a new formulation of BLP25 liposome vaccine in patients with unresectable stage III non-small-cell lung cancer.
    Clin Lung Cancer. 2010 Nov 1;11(6):391-5 PMID: 21071331
  75. Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis.
    Cancer Res. 2001 Nov 1;61(21):7959-63 PMID: 11691819
  76. Foxp3 expressing CD4+ CD25+ and CD8+CD28- T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma.
    Hum Immunol. 2006 Jan-Feb;67(1-2):1-12 PMID: 16698419
  77. Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients.
    J Immunol. 2004 Mar 1;172(5):3289-96 PMID: 14978137
  78. Expression of transforming growth factor beta ligand and receptor messenger RNAs in lung cancer cell lines.
    Cell Growth Differ. 1995 Apr;6(4):465-76 PMID: 7794814
  79. Successful immunotherapy with Mycobacterium vaccae in the treatment of adenocarcinoma of the lung.
    Eur J Cancer. 2008 Jan;44(2):224-7 PMID: 17928219
  80. Role of transforming growth factor beta in human disease.
    N Engl J Med. 2000 May 4;342(18):1350-8 PMID: 10793168
  81. Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.
    Cancer Immunol Immunother. 1996 Jun;42(5):303-9 PMID: 8706053
  82. Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activity.
    J Biomed Biotechnol. 2010;2010:798467 PMID: 20508851
  83. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40 PMID: 8552591
  84. Non-small cell lung cancer-derived soluble mediators and prostaglandin E2 enhance peripheral blood lymphocyte IL-10 transcription and protein production.
    J Immunol. 1996 Dec 15;157(12):5512-20 PMID: 8955201
  85. Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming.
    Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1650-5 PMID: 18216244
Article Info
Journal
The Lancet. Oncology
Abbr.
Lancet Oncol
ISSN
1474-5488
DOI
10.1016/S1470-2045(12)70126-2
Published
2012-07-00
Epub
2012-00-28
Pages
e301-10
Language
English
Region
England
NLM ID
100957246
PMCID
PMC6317076
Subset
IM
Grants
Intramural NIH HHS · Z99 CA999999 · United States
External Links
PubMed source DOI: 10.1016/S1470-2045(12)70126-2 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2