Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-29T02:26:42.167Z Has data issue: false hasContentIssue false
  • English
  • Français

Cell-based cancer gene therapy: breaking tolerance or inducing autoimmunity?

Published online by Cambridge University Press:  28 February 2007

Juan Carlos Rodriguez-Lecompte ,
Steve Kruth ,
Steve Gyorffy ,
Yong-Hong Wan  and
Jack Gauldie
Juan Carlos Rodriguez-Lecompte
Affiliation:
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaL8N 3Z5
Steve Kruth
Affiliation:
Ontario Veterinary College, Department of Clinical Studies, University of Guelph, Guelph, Ontario, CanadaN1G 2W1
Steve Gyorffy
Affiliation:
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaL8N 3Z5
Yong-Hong Wan
Affiliation:
Ontario Veterinary College, Department of Clinical Studies, University of Guelph, Guelph, Ontario, CanadaN1G 2W1
Jack Gauldie*
Affiliation:
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaL8N 3Z5
*
*Department of Pathology and Molecular Medicine, McMaster University, 1200 Main St W, Hamilton, Ontario, CanadaL8N 3Z5 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

This review examines the mechanisms involved in anti-tumor immunity and how peptides present in many tumor types (tumor-associated antigens) are recognized by T cells from tumor-bearing cancer patients. Tumor-associated antigens are derived from proteins that are also expressed in normal cells. It is predicted that immune responses to such peptides will be compromised by self-tolerance or that stimulation of effective immune responses will be accompanied by autoimmunity. We also consider that the immunity induced against two autoantigens, which are highly conserved in vertebrates, involve qualitatively different mechanisms, such as the production of antibodies and cell-mediated immune responses. However, both pathways lead to tumor immunity and identical phenotypic manifestations of autoimmunity. Appropriate selection of the optimal tumor antigen is critical for the induction of an anti-tumor immune response. Thus, we stress that the methods for antigen presentation using dendritic cells play a critical role in the development of tumor vaccines, to break immune tolerance and induce a strong immune response against them. The viability and feasibility of expansion of canine dendritic cells from bone marrow and peripheral blood ex vivo for the treatment of spontaneous cancers in dogs is also discussed.

Keywords

dendritic cellgene therapymelanomaautoimmunityimmunotherapytolerancecanineperipheral blood
Type
Research Article
Information
Animal Health Research Reviews , Volume 5 , Issue 2 , December 2004 , pp. 227 - 234
Copyright
Copyright © CAB International 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abbas, AK (2003). The control of T cell activation vs. tolerance. Autoimmunity Reviews 2: 115–118.CrossRefGoogle ScholarPubMed
Arnold, B (2002). Levels of peripheral T cell tolerance. Transplant Immunology 10: 109–114.Google Scholar
Banchereau, J, Briere, F, Caux, C, Davoust, J, Lebecque, S, Liu, YJ, Pulendran, B and Palucka, K (2000). Immunobiology of dendritic cells. Annual Review of Immunology 18: 767–811.CrossRefGoogle ScholarPubMed
Banchereau, J, Schuler-Thurner, B, Palucka, AK and Schuler, G (2001). Dendritic cells as vectors for therapy. Cell 106: 271–274.Google Scholar
Berinstein, N (2003). Overview of therapeutic vaccination approaches for cancer. Seminars in Oncology 30: 1–8.CrossRefGoogle ScholarPubMed
Bramson, JL and Wan, YH (2002). The efficacy of genetic vaccination is dependent upon the nature of the vector system and antigen. Expert Opinion on Biological Therapy 2: 75–85.Google Scholar
Brenner, MK (2001). Gene transfer and the treatment of haematological malignancy. Journal of Internal Medicine 249: 345–358.Google Scholar
Chamberlain, RS and Kaufman, H (2000). Innovations and strategies for the development of anticancer vaccines. Expert Opinion on Pharmacotherapy 1: 603–614.Google Scholar
Clark, GJ, Angel, N, Kato, M, Lopez, JA, MacDonald, K, Vuckovic, S and Hart, DN (2000). The role of dendritic cells in the innate immune system. Microbes and Infection 2: 257–272.Google Scholar
Eck, SC and Turka, LA (2001). Adoptive transfer enables tumour rejection targeted against a self-antigen without the induction of autoimmunity. Cancer Research 61: 3077–3083.Google Scholar
Engelhard, VH, Bullock, TN, Colella, TA, Sheasley, SL and Mullins, DW (2002). Antigens derived from melanocyte differentiation proteins: self-tolerance, autoimmunity, and use for cancer immunotherapy. Immunological Reviews 188: 136–146.Google Scholar
Engleman, EG (2003). Dendritic cell-based cancer immunotherapy. Seminars in Oncology 30: 23–29.Google Scholar
Engleman, EG and Fong, L (2003). Induction of immunity to tumour-associated antigens following dendritic cell vaccination of cancer patients. Clinical immunology 106: 10–15.Google Scholar
Fazekas de St Groth, B (2001). DCs and peripheral T cell tolerance. Seminars in Immunology 13: 311–322.CrossRefGoogle ScholarPubMed
Foley, R, Tozer, R and Wan, Y (2001). Genetically modified dendritic cells in cancer therapy: implications for transfusion medicine. Transfusion Medicine Reviews 15: 292–304.Google Scholar
Fong, L and Engleman, EG (2000). Dendritic cells in cancer immunotherapy. Annual Review of Immunology 18: 245–273.Google Scholar
Gilboa, E, Nair, SK and Lyerly, HK (1998). Immunotherapy of cancer with dendritic-cell-based vaccines. Cancer Immunology, Immunotherapy 46: 82–87.CrossRefGoogle ScholarPubMed
Gunzer, M and Grabbe, S (2001). Dendritic cells in cancer immunotherapy. Critical Reviews in Immunology 21: 133–145.Google ScholarPubMed
Gunzer, M, Janich, S, Varga, G and Grabbe, S (2001). Dendritic cells and tumour immunity. Seminars in Immunology 13: 291–302.Google Scholar
Gupta, S and Kanodia, AK (2002). Biological response modifiers in cancer therapy. National Medical Journal of India 15: 202–207.Google Scholar
Ludewig, B (2003). Dendritic cell vaccination and viral infection—animal models. Current Topics in Microbiology and Immunology. 276: 199–214.Google Scholar
Maldonado-Lopez, R and Moser, M (2001). Dendritic cell subsets and the regulation of Th1/Th2 responses. Seminars in Immunology 13:275–282.Google Scholar
McArthur, JG and Mulligan, RC (1998). Induction of protective anti-tumour immunity by gene-modified dendritic cells. Journal of Immunotherapy 21: 41–47.Google Scholar
Moser, M (2003). Dendritic cells in immunity and tolerance-do they display opposite functions? Immunity 19: 5–8.Google Scholar
Overwijk, WW, Lee, DS, Surman, DR, Irvine, KR, Touloukian, CE, Chan, CC, Carroll, MW, Moss, B, Rosenberg, SA and Restifo, NP (1999). Vaccination with a recombinant vaccinia virus encoding a ‘self’ antigen induces autoimmune vitiligo and tumour cell destruction in mice: requirement for CD4(+) T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 96: 2982–2987.Google Scholar
Platsoucas, CD, Fincke, JE, Pappas, J, Jung, WJ, Heckel, M, Schwarting, R, Magira, E, Monos, D and Freedman, RS (2003). Immune responses to human tumours: development of tumour vaccines. Anticancer Research 23: 1969–1996.Google Scholar
Rescigno, M (2002). Dendritic cells and the complexity of microbial infection. Trends in Microbiology 10: 425–461.CrossRefGoogle ScholarPubMed
Schreurs, MW, Eggert, AA, de Boer, AJ, Vissers, JL, van Hall, T, Offringa, R, Figdor, CG and Adema, GJ (2000). Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model. Cancer Research 60: 6995–7001.Google Scholar
Schweighoffer, T (1996). Tumour cells expressing a recall antigen are powerful cancer vaccines. European Journal of Immunology 26: 2559–2564.CrossRefGoogle ScholarPubMed
Sozzani, S, Allavena, P, Vecchi, A and Mantovani, A (2000). Chemokines and dendritic cell traffic. Journal of Clinical Immunology 20: 151–160.Google Scholar
Timmerman, JM and Levy, R (1999). Dendritic cell vaccines for cancer immunotherapy. Annual Review of Medicine 50: 507–529.Google Scholar
Wan, Y, Lu, L, Bramson, JL, Baral, S, Zhu, Q, Pilon, A and Dayball, K (2001). Dendritic cell-derived IL-12 is not required for the generation of cytotoxic, IFN-gamma-secreting, CD8(+) CTL in vivo. Journal of Immunology 167: 5027–5033.Google Scholar
Wang, RF (2002). Enhancing antitumour immune responses: intracellular peptide delivery and identification of MHC class II-restricted tumour antigens. Immunological Reviews 188: 65–80.Google Scholar
Ward, S, Casey, D, Labarthe, MC, Whelan, M, Dalgleish, A, Pandha, H and Todryk, S (2002). Immunotherapeutic potential of whole tumour cells. Cancer Immunology, Immunotherapy 51: 351–357.Google Scholar
Yang, S, Vervaert, CE, Burch, J, Grichnik, J Jr, Seigler, HF and Darrow, TL (1999). Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8(+) and CD4(+) T-cell responses and are more effective than DNA vaccines at generating anti-tumour immunity. International Journal of Cancer 83: 532–540.Google Scholar
Zeuthen, J, Dzhandzhugazyan, K, Hansen, MR and Kirkin, AF (1998). The immunogenic properties of human melanomas and melanoma-associated antigens recognized by cytotoxic T lymphocytes. Bratislavske Lekarske Listy 99: 426–434.Google Scholar
Zhou, Y, Bosch, ML and Salgaller, ML (2002). Current methods for loading dendritic cells with tumour antigen for the induction of antitumour immunity. Journal of Immunotherapy 25: 289–303.Google Scholar