Advertisement

Cancer Vaccines

Chapter

The role of the immune system in preventing the development of tumours was first suggested by Paul Ehrlich in the early 1900s. Half a century later, Lewis Thomas and McFarlaine Burnet introduced the concept of immunosurveillance, meaning that immune cells while continuously patrolling the body recognise special antigens present only on transformed cells and eliminate these cells. They suggested that the type of cell responsible for tumour immunosurveillance is the T cell [1]. Direct experimental evidence confirming this hypothesis came from immunodeficient mouse strains, where the lack of certain components of the cellular immune response, such as interferon (IFN)-γ, perforin, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), lead to significantly more aggressive growth of experimental tumours [2]. More importantly, late onset of spontaneously occurring adenocarcinoma has been observed in IFN-γ and perforin-deficient mice [3]. Indirect evidence in humans is the survival benefit of cancer patients with tumours infiltrated with activated CD8+ T cells, observed in numerous cancers such as ovarian, prostate, colorectal, and mesothelioma [4–8].

Keywords

Major Histocompatibility Complex Class Treg Cell Tumour Antigen Cancer Vaccine Chimeric Antigen Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

The author thanks Mr B. Keszei for his assistance with the illustrations.

References

  1. 1.
    Burnet FM. Immunological aspects of malignant disease. Lancet 1967; 1: 1171–1174.PubMedCrossRefGoogle Scholar
  2. 2.
    Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 2001; 97: 192–197.PubMedCrossRefGoogle Scholar
  3. 3.
    Street SE, Trapani JA, MacGregor D, Smyth MJ. Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med 2002; 196: 129–134.PubMedCrossRefGoogle Scholar
  4. 4.
    Sato E et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 2005; 102: 18538–18543.PubMedCrossRefGoogle Scholar
  5. 5.
    Kärjä V et al. Tumour-infiltrating lymphocytes: A prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res 2005; 25: 4435–4438.PubMedGoogle Scholar
  6. 6.
    Galon J et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313: 1960–1964.PubMedCrossRefGoogle Scholar
  7. 7.
    Anraku M et al. Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2008; 135: 823–829.PubMedCrossRefGoogle Scholar
  8. 8.
    Leffers N et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother 2008; doi: 10.1007/s0026200805835.Google Scholar
  9. 9.
    Dunn GP et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3: 991–998.PubMedCrossRefGoogle Scholar
  10. 10.
    Gattinoni L et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest 2005; 115: 1616–1626.PubMedCrossRefGoogle Scholar
  11. 11.
    Dudley ME et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005; 23: 2346–2357.PubMedCrossRefGoogle Scholar
  12. 12.
    Rosenberg SA et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008; 8: 299–308.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhou J et al. Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy. J Immunol 2005; 175: 7046–7052.PubMedGoogle Scholar
  14. 14.
    Powell DJ et al. Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion. J Immunol 2006; 177: 6527–6539.PubMedGoogle Scholar
  15. 15.
    Liu S, Riley J, Rosenberg S, Parkhurst M. Comparison of common gamma-chain cytokines, interleukin-2, interleukin-7, and interleukin-15 for the in vitro generation of human tumor-reactive T lymphocytes for adoptive cell transfer therapy. J Immunother 2006; 29: 284–293.PubMedCrossRefGoogle Scholar
  16. 16.
    Hinrichs CS et al. IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 2008; 111: 5326–5333.PubMedCrossRefGoogle Scholar
  17. 17.
    Müller-Hermelink N et al. TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 2008; 13: 507–518.PubMedCrossRefGoogle Scholar
  18. 18.
    Perez-Diez A et al. CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood 2007; 109: 5346–5354.PubMedCrossRefGoogle Scholar
  19. 19.
    Benchetrit F et al. Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood 2002; 99: 2114–2121.PubMedCrossRefGoogle Scholar
  20. 20.
    Muranski P et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 2008; 112: 362–373.PubMedCrossRefGoogle Scholar
  21. 21.
    Nam JS et al. Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 2008; 68: 3915–3923.PubMedCrossRefGoogle Scholar
  22. 22.
    Dudley ME et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298: 850–854.PubMedCrossRefGoogle Scholar
  23. 23.
    Wrzesinski C et al. Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8 T cells. J Clin Invest 2007; 117: 492–501.PubMedCrossRefGoogle Scholar
  24. 24.
    Perera LP et al. Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. J Virol 2007; 81: 8774–8783.PubMedCrossRefGoogle Scholar
  25. 25.
    Sato N, Patel HJ, Waldmann TA, Tagaya Y. The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells. Proc Natl Acad Sci USA 2007; 104: 588–593.PubMedCrossRefGoogle Scholar
  26. 26.
    Colombo MP, Piconese S. Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer 2007; 7: 880–887.PubMedCrossRefGoogle Scholar
  27. 27.
    Morgan RA et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–129.PubMedCrossRefGoogle Scholar
  28. 28.
    Cohen CJ et al. Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res 2007; 67: 3898–3903.PubMedCrossRefGoogle Scholar
  29. 29.
    Morgenroth A et al. Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells. Prostate 2007; 67: 1121–1131.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhao Y et al. Extrathymic generation of tumor-specific T cells from genetically engineered human hematopoietic stem cells via Notch signaling. Cancer Res 2007; 67: 2425–2429.PubMedCrossRefGoogle Scholar
  31. 31.
    Gattinoni L, Powell DJ, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 2006; 6: 383–393.PubMedCrossRefGoogle Scholar
  32. 32.
    Rubinstein MP et al. Loss of T cell-mediated antitumor immunity after construct-specific downregulation of retrovirally encoded T-cell receptor expression in vivo. Cancer Gene Ther 2009; 16: 171–183.Google Scholar
  33. 33.
    Sadelain M, Rivière I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer 2003; 3: 35–45.PubMedCrossRefGoogle Scholar
  34. 34.
    Gade TP et al. Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer Res 2005; 65: 9080–9088.PubMedCrossRefGoogle Scholar
  35. 35.
    Fujita M et al. Inhibition of STAT3 promotes the efficacy of adoptive transfer therapy using type-1 CTLs by modulation of the immunological microenvironment in a murine intracranial glioma. J Immunol 2008; 180: 2089–2098.PubMedGoogle Scholar
  36. 36.
    Ghiringhelli F et al. Tumor cells convert immature myeloid dendritic cells into TGF-{beta}-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med 2005; 202: 919–929.PubMedCrossRefGoogle Scholar
  37. 37.
    Dohnal AM et al. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines. J Cell Mol Med 2008: E-pub.Google Scholar
  38. 38.
    Curti A et al. Dendritic cell differentiation from hematopoietic CD34+ progenitor cells. J Biol Regul Homeost Agents 2001; 15: 49–52.PubMedGoogle Scholar
  39. 39.
    Trakatelli M et al. A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients. Cancer Immunol Immunother 2006; 55: 469–474.PubMedCrossRefGoogle Scholar
  40. 40.
    Banchereau J, Pascual V, Palucka AK. Autoimmunity through cytokine-induced dendritic cell activation. Immunity 2004; 20: 539–550.PubMedCrossRefGoogle Scholar
  41. 41.
    Iwamoto S et al. TNF-alpha drives human CD14+ monocytes to differentiate into CD70+ dendritic cells evoking Th1 and Th17 responses. J Immunol 2007; 179: 1449–1457.PubMedGoogle Scholar
  42. 42.
    Bharadwaj U et al. Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation. Cancer Res 2007; 67: 5479–5488.PubMedCrossRefGoogle Scholar
  43. 43.
    Ratta M et al. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 2002; 100: 230–237.PubMedCrossRefGoogle Scholar
  44. 44.
    Pinzon-Charry A et al. Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer. Br J Cancer 2007; 97: 1251–1259.PubMedCrossRefGoogle Scholar
  45. 45.
    Jonuleit H et al. A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 2001; 93: 243–251.PubMedCrossRefGoogle Scholar
  46. 46.
    Nicolette CA et al. Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products. Vaccine 2007; 25: S2 B47–60.CrossRefGoogle Scholar
  47. 47.
    Czerniecki BJ et al. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res 2007; 67: 1842–1852.PubMedCrossRefGoogle Scholar
  48. 48.
    Tong AW, Stone MJ. Prospects for CD40-directed experimental therapy of human cancer. Cancer Gene Ther 2003; 10: 1–13.PubMedCrossRefGoogle Scholar
  49. 49.
    Nestle FO et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998; 4: 328–332.PubMedCrossRefGoogle Scholar
  50. 50.
    Hatfield P et al. Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J Immunother 2008; 31: 620–632.PubMedCrossRefGoogle Scholar
  51. 51.
    Obeid M et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 2007; 13: 54–61.PubMedCrossRefGoogle Scholar
  52. 52.
    Obeid M et al. Calreticulin exposure is required for the immunogenicity of gamma-irradiation and UVC light-induced apoptosis. Cell Death Differ 2007; 14: 1848–1850.Google Scholar
  53. 53.
    Fay JW et al. Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34(+) progenitor-derived dendritic cells. Cancer Immunol Immunother 2006; 55: 1209–1218.PubMedCrossRefGoogle Scholar
  54. 54.
    Miura S et al. Appropriate timing of CD40 ligation for RNA-Pulsed DCs to induce antitumor immunity. Scand J Immunol 2008; 67: 385–391.PubMedCrossRefGoogle Scholar
  55. 55.
    Michiels A et al. Delivery of tumor-antigen-encoding mRNA into dendritic cells for vaccination. Methods Mol Biol 2008; 423: 155–163.PubMedCrossRefGoogle Scholar
  56. 56.
    Bonifaz L et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 2002; 196: 1627–1638.PubMedCrossRefGoogle Scholar
  57. 57.
    Tacken PJ et al. Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody. Blood 2005; 106: 1278–1285.PubMedCrossRefGoogle Scholar
  58. 58.
    Fong L et al. Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 2001; 166: 4254–4259.PubMedGoogle Scholar
  59. 59.
    Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 1997; 3: 558–561.PubMedCrossRefGoogle Scholar
  60. 60.
    Vasir B et al. Fusions of dendritic cells with breast carcinoma stimulate the expansion of regulatory T cells while concomitant exposure to IL-12, CpG oligodeoxynucleotides, and anti-CD3/CD28 promotes the expansion of activated tumor reactive cells. J Immunol 2008; 181: 808–821.PubMedGoogle Scholar
  61. 61.
    Zhang M, Berndt BE, Chen JJ, Kao JY. Expression of a soluble TGF-beta receptor by tumor cells enhances dendritic cell/tumor fusion vaccine efficacy. J Immunol 2008; 181: 3690–3697.PubMedGoogle Scholar
  62. 62.
    Lienard D et al. Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA. Cancer Immun 2004; 4: 4.PubMedGoogle Scholar
  63. 63.
    Zeng G et al. Generation of NY-ESO-1-specific CD4+ and CD8+ T cells by a single peptide with dual MHC class I and class II specificities: a new strategy for vaccine design. Cancer Res 2002; 62: 3630–3635.PubMedGoogle Scholar
  64. 64.
    Knutson K, Schiffman K, Disis M. Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients. J Clin Invest 2001; 107: 477–484.PubMedCrossRefGoogle Scholar
  65. 65.
    Gnjatic S et al. CD8(+) T cell responses against a dominant cryptic HLA-A2 epitope after NY-ESO-1 peptide immunization of cancer patients. Proc Natl Acad Sci USA 2002; 99: 11813–11818.PubMedCrossRefGoogle Scholar
  66. 66.
    van der Burg SH et al. Improved peptide vaccine strategies, creating synthetic artificial infections to maximize immune efficacy. Adv Drug Deliv Rev 2006; 58: 916–930.PubMedCrossRefGoogle Scholar
  67. 67.
    Ahonen CL et al. Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J Exp Med 2004; 199: 775–784.PubMedCrossRefGoogle Scholar
  68. 68.
    Roth A et al. Induction of effective and antigen-specific antitumour immunity by a liposomal ErbB2/HER2 peptide-based vaccination construct. Br J Cancer 2005; 92: 1421–1429.PubMedCrossRefGoogle Scholar
  69. 69.
    Valmori D et al. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc Natl Acad Sci USA 2007; 104: 8947–8952.PubMedCrossRefGoogle Scholar
  70. 70.
    Harrop R, John J, Carroll MW. Recombinant viral vectors: cancer vaccines. Adv Drug Deliv Rev 2006; 58: 931–947.PubMedCrossRefGoogle Scholar
  71. 71.
    Arlen PM et al. Preclinical and clinical studies of recombinant poxvirus vaccines for carcinoma therapy. Crit Rev Immunol 2007; 27: 451–462.PubMedGoogle Scholar
  72. 72.
    Lindsey KR et al. Evaluation of prime/boost regimens using recombinant poxvirus/tyrosinase vaccines for the treatment of patients with metastatic melanoma. Clin Cancer Res 2006; 12: 2526–2537.PubMedCrossRefGoogle Scholar
  73. 73.
    Kaufman HL et al. Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. J Transl Med 2007; 5: 60.PubMedCrossRefGoogle Scholar
  74. 74.
    Adamina M et al. Heterologous prime-boost immunotherapy of melanoma patients with Influenza virosomes, and recombinant Vaccinia virus encoding 5 melanoma epitopes and 3 co-stimulatory molecules. A multi-centre phase I/II open labeled clinical trial. Contemp Clin Trials 2008; 29: 165–181.PubMedCrossRefGoogle Scholar
  75. 75.
    Hallermalm K et al. Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer. Scand J Immunol 2007; 66: 43–51.PubMedCrossRefGoogle Scholar
  76. 76.
    Doehn C et al. Drug evaluation: Therion's rV-PSA-TRICOM + rF-PSA-TRICOM prime-boost prostate cancer vaccine. Curr Opin Mol Ther 2007; 9: 183–189.PubMedGoogle Scholar
  77. 77.
    Jäger E et al. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proc Natl Acad Sci USA 2006; 103: 14453–14458.PubMedCrossRefGoogle Scholar
  78. 78.
    Fiander AN et al. Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial. Int J Gynecol Cancer 2006; 16: 1075–1081.PubMedCrossRefGoogle Scholar
  79. 79.
    Skene CD, Sutton P. Saponin-adjuvanted particulate vaccines for clinical use. Methods 2006; 40: 53–59.PubMedCrossRefGoogle Scholar
  80. 80.
    Downey SG et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res 2007; 13: 6681–6688.PubMedCrossRefGoogle Scholar
  81. 81.
    Loskog A, Tötterman TH. CD40L - a multipotent molecule for tumor therapy. Endocr Metab Immune Disord Drug Targets 2007; 7: 23–28.PubMedGoogle Scholar
  82. 82.
    Fattorossi A et al. Neoadjuvant therapy changes the lymphocyte composition of tumor-draining lymph nodes in cervical carcinoma. Cancer 2004; 100: 1418–1428.PubMedCrossRefGoogle Scholar
  83. 83.
    Coleman S et al. Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer. Cancer Res 2005; 65: 7000–7006.PubMedCrossRefGoogle Scholar
  84. 84.
    Okada H, Mak TW. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 2004; 4: 592–603.PubMedCrossRefGoogle Scholar
  85. 85.
    Bang S et al. Differences in immune cells engaged in cell-mediated immunity after chemotherapy for far advanced pancreatic cancer. Pancreas 2006; 32: 29–36.PubMedCrossRefGoogle Scholar
  86. 86.
    Nowak AK, Lake RA, Robinson BW. Combined chemoimmunotherapy of solid tumours: improving vaccines? Adv Drug Deliv Rev 2006; 58: 975–990.PubMedCrossRefGoogle Scholar
  87. 87.
    Beyer M et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 2005; 106: 2018–2025.PubMedCrossRefGoogle Scholar
  88. 88.
    Audia S et al. Increase of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+ CD25+ T lymphocytes. Clin Exp Immunol 2007; 150: 523–530.PubMedCrossRefGoogle Scholar
  89. 89.
    Brode S, Raine T, Zaccone P, Cooke A. Cyclophosphamide-induced type-1 diabetes in the NOD mouse is associated with a reduction of CD4+CD25+Foxp3+ regulatory T cells. J Immunol 2006; 177: 6603–6612.PubMedGoogle Scholar
  90. 90.
    Mozaffari F et al. NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy. Br J Cancer 2007; 97: 105–111.PubMedCrossRefGoogle Scholar
  91. 91.
    Santin AD et al. Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix. Int J Radiat Oncol Biol Phys 2000; 48: 997–1006.PubMedCrossRefGoogle Scholar
  92. 92.
    Chakraborty M et al. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res 2004; 64: 4328–4337.PubMedCrossRefGoogle Scholar
  93. 93.
    Garnett CT et al. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res 2004; 64: 7985–7994.PubMedCrossRefGoogle Scholar
  94. 94.
    Reits EA et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 2006; 203: 1259–1271.Google Scholar
  95. 95.
    Apetoh L et al. The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol Rev 2007; 220: 47–59.PubMedCrossRefGoogle Scholar
  96. 96.
    Nesslinger NJ et al. Standard Treatments Induce Antigen-Specific Immune Responses in Prostate Cancer. Clin Cancer Res 2007; 13: 1493–1502.PubMedCrossRefGoogle Scholar
  97. 97.
    Mason KA et al. Targeting toll-like receptor 9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy. Clin Cancer Res 2005; 11: 361–369.PubMedGoogle Scholar
  98. 98.
    Gulley JL et al. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res 2005; 11: 3353–3362.PubMedCrossRefGoogle Scholar
  99. 99.
    Tabi Z et al. Memory T Cell Resistance to Functional Impairment and Apoptosis During Radiation Therapy in Cancer. Unpublished.Google Scholar
  100. 100.
    Small EJ et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 2000; 18: 3894–3903.PubMedGoogle Scholar
  101. 101.
    Burch PA et al. Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer: a Phase 2 trial. Prostate 2004; 60: 197–204.PubMedCrossRefGoogle Scholar
  102. 102.
    Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in non small cell lung cancer. Clin Cancer Res 2007; 13: s4652–4654.PubMedCrossRefGoogle Scholar
  103. 103.
    North SA, Graham K, Bodnar D, Venner P. A pilot study of the liposomal MUC1 vaccine BLP25 in prostate specific antigen failures after radical prostatectomy. J Urol 2006; 176: 91–95.PubMedCrossRefGoogle Scholar
  104. 104.
    Southall PJ et al. Immunohistological distribution of 5T4 antigen in normal and malignant tissues. Br J Cancer 1990; 61: 89–95.PubMedCrossRefGoogle Scholar
  105. 105.
    Harrop R et al. Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) induces immune responses which correlate with disease control: a phase I/II trial. Clin Cancer Res 2006; 12: 3416–3424.PubMedCrossRefGoogle Scholar
  106. 106.
    Amato RJ et al. Vaccination of prostate cancer patients with modified vaccinia ankara delivering the tumor antigen 5T4 (TroVax): a phase 2 trial. J Immunother 2008; 31: 577–585.PubMedCrossRefGoogle Scholar
  107. 107.
    Madan RA et al. Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy. Clin Cancer Res 2008; 14: 4526–4531.PubMedCrossRefGoogle Scholar
  108. 108.
    Nemunaitis J et al. 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; 24: 4721–4730.PubMedCrossRefGoogle Scholar
  109. 109.
    Phatak P et al. Telomere uncapping by the G-quadruplex ligand RHPS4 inhibits clonogenic tumour cell growth in vitro and in vivo consistent with a cancer stem cell targeting mechanism. Br J Cancer 2007; 96: 1223–1233.PubMedCrossRefGoogle Scholar
  110. 110.
    Cortez-Gonzalez X, Zanetti M. Telomerase immunity from bench to bedside: round one. J Transl Med 2007; 5: 12.PubMedCrossRefGoogle Scholar
  111. 111.
    Wood C et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 2008; 372: 145–154.PubMedCrossRefGoogle Scholar
  112. 112.
    Testori A et al. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol 2008; 26: 955–962.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of OncologySchool of Medicine, Cardiff University, Velindre Hospital, WhitchurchCardiffUK

Personalised recommendations