Advertisement

Current Colorectal Cancer Reports

, Volume 9, Issue 4, pp 380–390 | Cite as

Status of Active Specific Immunotherapy for Stage II, Stage III, and Resected Stage IV Colon Cancer

  • Vanessa DeschoolmeesterEmail author
  • Evelien Smits
  • Marc Peeters
  • Jan B. Vermorken
Immunotherapy of Malignancy (MA Morse, Section Editor)

Abstract

Colorectal cancer is one of the most prevalent types of cancer worldwide and a leading cause of cancer-related mortality. The reported incidence of recurrent disease increases with the stage, and the 5-year survival rate is poor, especially for tumors with regional spread and for late-stage disease. This has prompted the search for more advanced treatment options, and therefore avenues for clinical testing of rationally designed immunotherapeutic strategies, including vaccination, as adjuvant treatment are being explored. In this review, we discuss the study design and results of the clinical trials that have been conducted using active specific immunotherapy in colorectal cancer, including autologous and allogeneic tumor cell vaccines, peptide vaccines, viral-vector-based vaccines, and dendritic-cell-based vaccines as well as some future recommendations.

Keywords

Active specific immunotherapy Colon cancer Clinical trials Immune cells T cells Vaccine Viral vector vaccines Dendritic cell vaccines Peptide vaccines Allogeneic whole tumor cell vaccines Autologous tumor cell vaccines 

Notes

Compliance with ethics Guidelines

Conflict of Interest

Vanessa Deschoolmeester, Evelien Smits, and Marc Peeters declare that they have no conflict of interest.

Jan B. Vermorken has served as a board member for Vaccinogen, has received payment for lectures, including service on speakers bureaus, from Merck Serono, and has received compensation for the development of educational presentations from Bristol-Myers Squibb.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Okuno K, Sugiura F, Itoh K, Yoshida K, Tsunoda T, Nakamura Y. Recent advances in active specific cancer vaccine treatment for colorectal cancer. Curr Pharm Biotechnol. 2012;13:1439–45.CrossRefPubMedGoogle Scholar
  3. 3.
    Uyl-de Groot CA, Vermorken JB, Hanna MG, et al. Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits. Vaccine. 2005;23:2379–87.CrossRefPubMedGoogle Scholar
  4. 4.
    • Speetjens FM, Zeestraten EC, Kuppen PJ, Melief CJ, van der Burg SH. Colorectal cancer vaccines in clinical trials. Expert Rev Vaccines. 2011;10:899–921. The authors elucidate current strategies of ASI for CRC patients with a focus on T-cell-mediated immunotherapy. They refer to clinical trials using either tumor-cell-derived vaccines or tumor antigen vaccines.CrossRefPubMedGoogle Scholar
  5. 5.
    Hellinger MD, Santiago CA. Reoperation for recurrent colorectal cancer. Clin Colon Rectal Surg. 2006;19:228–36.CrossRefPubMedGoogle Scholar
  6. 6.
    Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken JB. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist. 2010;15:699–731.CrossRefPubMedGoogle Scholar
  7. 7.
    Rao B, Han M, Wang L, et al. Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review. J Transl Med. 2011;9:17.CrossRefPubMedGoogle Scholar
  8. 8.
    Nair SK, Morse M, Boczkowski D, et al. Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. Ann Surg. 2002;235:540–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Pagès F, Galon J, Fridman WH. The essential role of the in situ immune reaction in human colorectal cancer. J Leukoc Biol. 2008;84:981–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Loose D, Van de Wiele C. The immune system and cancer. Cancer Biother Radiopharm. 2009;24:369–76.CrossRefPubMedGoogle Scholar
  11. 11.
    Watson NFS, Ramage JM, Madjd Z, Spendlove I, Ellis IO, Scholefield JH, et al. Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis. Int J Cancer. 2006;118:6–10.CrossRefPubMedGoogle Scholar
  12. 12.
    Titu LV, Monson JRT, Greenman J. The role of CD8+ T cells in immune responses to colorectal cancer. Cancer Immunol Immunother. 2002;51:235–47.CrossRefPubMedGoogle Scholar
  13. 13.
    Atkinson EA, Bleackley RC. Mechanisms of lysis by cytotoxic T cells. Crit Rev Immunol. 1995;15:359–84.CrossRefPubMedGoogle Scholar
  14. 14.
    Deschoolmeester V, Baay M, Lardon F, Pauwels P, Peeters M. Immune cells in colorectal cancer: prognostic relevance and role of MSI. Cancer Microenviron. 2011;4:377–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Gershon RK, Kondo K. Infectious immunological tolerance. Immunology. 1971;21:903–14.PubMedGoogle Scholar
  16. 16.
    Gershon RK, Cohen P, Hencin R, Liebhaber SA. Suppressor T cells. J Immunol. 1972;108:586–90.PubMedGoogle Scholar
  17. 17.
    Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155:1151–64.PubMedGoogle Scholar
  18. 18.
    Suzuki H, Chikazawa N, Tasaka T, et al. Intratumoral CD8+ T/FOXP3+ cell ratio is a predictive marker for survival in patients with colorectal cancer. Cancer Immunol Immunother. 2010;59:653–61.CrossRefPubMedGoogle Scholar
  19. 19.
    Schwitalle Y, Kloor M, Eiermann S, et al. Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology. 2008;134:988–97.CrossRefPubMedGoogle Scholar
  20. 20.
    Sinicrope FA, Rego RL, Ansell SM, Knutson KL, Foster NR, Sargent DJ. Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology. 2009;137:1270–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Loddenkemper C, Schernus M, Noutsias M, Stein H, Thiel E, Nagorsen D. In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer. J Transl Med. 2006;4:52.CrossRefPubMedGoogle Scholar
  22. 22.
    Hanna MG, Hoover HC, Peters LC. Immunotherapy by active specific immunization: basic principles and preclinical studies. In: DeVita VT, Hellman S, Rosenberg SA, editors. Biologic therapy of cancer. Philadelphia: Lippincott; 1991. p. 651–69.Google Scholar
  23. 23.
    Walzer T, Dalod M, Vivier E, Zitvogel L. Natural killer cell-dendritic cell crosstalk in the initiation of immune responses. Expert Opin Biol Ther. 2005;5 Suppl 1:S49–59.CrossRefPubMedGoogle Scholar
  24. 24.
    Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15:5323–37.CrossRefPubMedGoogle Scholar
  25. 25.
    Hanna MG, Hoover HC, Pinedo HM, Finer M. Active specific immunotherapy with autologous tumor cell vaccines for stage II colon cancer: logistics, efficacy, safety and immunological pharmacodynamics. Hum Vaccines. 2006;2:185–91.CrossRefGoogle Scholar
  26. 26.
    Hanna MG, Peters LC. Specific immunotherapy of established visceral micrometastases by BCG-tumor cell vaccine alone or as an adjunct to surgery. Cancer. 1978;42:2613–25.CrossRefPubMedGoogle Scholar
  27. 27.
    Vermorken JB, Claessen AM, van Tinteren H, et al. Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet. 1999;353:345–50.CrossRefPubMedGoogle Scholar
  28. 28.
    Harris JE, Ryan L, Hoover HC, et al. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Oncol. 2000;18:148–57.PubMedGoogle Scholar
  29. 29.
    Hoover HC, Surdyke M, Dangel RB, Peters LC, Hanna MG. Delayed cutaneous hypersensitivity to autologous tumor cells in colorectal cancer patients immunized with an autologous tumor cell: bacillus Calmette-Guérin vaccine. Cancer Res. 1984;44:1671–6.PubMedGoogle Scholar
  30. 30.
    Hoover HC, Surdyke MG, Dangel RB, Peters LC, Hanna MG. Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer. Cancer. 1985;55:1236–43.CrossRefPubMedGoogle Scholar
  31. 31.
    Hoover HC, Brandhorst JS, Peters LC, et al. Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial. J Clin Oncol. 1993;11:390–9.PubMedGoogle Scholar
  32. 32.
    Liang W, Wang H, Sun T-M, et al. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive tract. World J Gastroenterol. 2003;9:495–8.PubMedGoogle Scholar
  33. 33.
    Schulze T, Kemmner W, Weitz J, Wernecke K-D, Schirrmacher V, Schlag PM. Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: results of a prospective randomized trial. Cancer Immunol Immunother. 2009;58:61–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Ockert D, Schirrmacher V, Beck N, Stoelben E, Ahlert T, Flechtenmacher J, et al. Newcastle disease virus-infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma. Clin. Cancer Res. 1996 ;2(1):21–8.Google Scholar
  35. 35.
    •• de Weger VA, Turksma AW, Voorham QJM, et al. Clinical effects of adjuvant active specific immunotherapy differ between patients with microsatellite-stable and microsatellite-instable colon cancer. Clin Cancer Res. 2012;18:882–9. The authors show the robustness of the clinical benefit of OncoVax in colon cancer patients by a review of the follow-up of patients. The significant benefit in recurrence-free survival measured at 5 years was reevaluated and confirmed at 15 years’ follow-up.CrossRefPubMedGoogle Scholar
  36. 36.
    Ravindranath MH, Morton DL. Active specific immunotherapy with vaccines. In: Bast Jr RC, Kufe DW, Pollock RE, editors. Holland-Frei cancer medicine. 5th ed. Hamilton: BC Decker; 2000.Google Scholar
  37. 37.
    Correale P, Cusi MG, Tsang K-Y, et al. Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients. J Clin Oncol. 2005;23:8950–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Baars A, Claessen AME, Wagstaff J, et al. A phase II study of active specific immunotherapy and 5-FU/leucovorin as adjuvant therapy for stage III colon carcinoma. Br J Cancer. 2002;86:1230–4.CrossRefPubMedGoogle Scholar
  39. 39.
    Woodlock TJ, Sahasrabudhe DM, Marquis DM, Greene D, Pandya KJ, McCune CS. Active specific immunotherapy for metastatic colorectal carcinoma: phase I study of an allogeneic cell vaccine plus low-dose interleukin-1 alpha. J Immunother. 1999;22:251–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Shawler DL, Bartholomew RM, Garrett MA, et al. Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine. Clin Exp Immunol. 2002;129:99–106.CrossRefPubMedGoogle Scholar
  41. 41.
    Habal N, Gupta RK, Bilchik AJ, et al. CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer. Ann Surg Oncol. 2001;8:389–401.CrossRefPubMedGoogle Scholar
  42. 42.
    Merika E, Saif MW, Katz A, Syrigos K, Syrigos C, Morse M. Review. Colon cancer vaccines: an update. In Vivo. 2010;24:607–28.PubMedGoogle Scholar
  43. 43.
    Weihrauch MR, Ansén S, Jurkiewicz E, et al. Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. Clin Cancer Res. 2005;11:5993–6001.CrossRefPubMedGoogle Scholar
  44. 44.
    Tsuruma T, Hata F, Torigoe T, et al. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. J Transl Med. 2004;2:19.CrossRefPubMedGoogle Scholar
  45. 45.
    Miyagi Y, Imai N, Sasatomi T, et al. Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides. Clin Cancer Res. 2001;7:3950–62.PubMedGoogle Scholar
  46. 46.
    Hattori T, Mine T, Komatsu N, et al. Immunological evaluation of personalized peptide vaccination in combination with UFT and UZEL for metastatic colorectal carcinoma patients. Cancer Immunol Immunother. 2009;58:1843–52.CrossRefPubMedGoogle Scholar
  47. 47.
    Sato Y, Fujiwara T, Mine T, et al. Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients. Cancer Sci. 2007;98:1113–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Sato Y, Maeda Y, Shomura H, et al. A phase I trial of cytotoxic T-lymphocyte precursor-oriented peptide vaccines for colorectal carcinoma patients. Br J Cancer. 2004;90:1334–42.CrossRefPubMedGoogle Scholar
  49. 49.
    Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–15.CrossRefPubMedGoogle Scholar
  50. 50.
    Speetjens FM, Kuppen PJK, Welters MJP, et al. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clin Cancer Res. 2009;15:1086–95.CrossRefPubMedGoogle Scholar
  51. 51.
    Yamada A, Sasada T, Noguchi M, Itoh K. Next-generation peptide vaccines for advanced cancer. Cancer Sci. 2013;104:15–21.CrossRefPubMedGoogle Scholar
  52. 52.
    Goydos JS, Elder E, Whiteside TL, Finn OJ, Lotze MT. A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. J Surg Res. 1996;63:298–304.CrossRefPubMedGoogle Scholar
  53. 53.
    Khleif SN, Abrams SI, Hamilton JM, et al. A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors. J Immunother. 1999;22:155–65.CrossRefPubMedGoogle Scholar
  54. 54.
    Moulton HM, Yoshihara PH, Mason DH, Iversen PL, Triozzi PL. Active specific immunotherapy with a beta-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: antibody response is associated with improved survival. Clin Cancer Res. 2002;8:2044–51.PubMedGoogle Scholar
  55. 55.
    Morse MA, Deng Y, Coleman D, et al. A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res. 1999;5:1331–8.PubMedGoogle Scholar
  56. 56.
    Fong L, Hou Y, Rivas A, et al. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci U S A. 2001;98:8809–14.CrossRefPubMedGoogle Scholar
  57. 57.
    Rains N, Cannan RJ, Chen W, Stubbs RS. Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer. Hepatogastroenterology. 2001;48:347–51.PubMedGoogle Scholar
  58. 58.
    Sadanaga N, Nagashima H, Mashino K, et al. Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res. 2001;7:2277–84.PubMedGoogle Scholar
  59. 59.
    Toungouz M, Libin M, Bulté F, et al. Transient expansion of peptide-specific lymphocytes producing IFN-gamma after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage-A1/A3-positive tumors. J Leukoc Biol. 2001;69:937–43.PubMedGoogle Scholar
  60. 60.
    Itoh T, Ueda Y, Kawashima I, et al. Immunotherapy of solid cancer using dendritic cells pulsed with the HLA-A24-restricted peptide of carcinoembryonic antigen. Cancer Immunol Immunother. 2002;51:99–106.CrossRefPubMedGoogle Scholar
  61. 61.
    Morse MA, Nair SK, Mosca PJ, et al. Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA. Cancer Invest. 2003;21:341–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Liu K-J, Wang C-C, Chen L-T, et al. Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides. Clin Cancer Res. 2004;10:2645–51.CrossRefPubMedGoogle Scholar
  63. 63.
    Matsuda K, Tsunoda T, Tanaka H, et al. Enhancement of cytotoxic T-lymphocyte responses in patients with gastrointestinal malignancies following vaccination with CEA peptide-pulsed dendritic cells. Cancer Immunol Immunother. 2004;53:609–16.CrossRefPubMedGoogle Scholar
  64. 64.
    Ueda Y, Itoh T, Nukaya I, et al. Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas. Int J Oncol. 2004;24:909–17.PubMedGoogle Scholar
  65. 65.
    Morse MA, Clay TM, Hobeika AC, et al. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin Cancer Res. 2005;11:3017–24.CrossRefPubMedGoogle Scholar
  66. 66.
    Babatz J, Röllig C, Löbel B, et al. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells. Cancer Immunol Immunother. 2006;55:268–76.CrossRefPubMedGoogle Scholar
  67. 67.
    Burgdorf SK, Fischer A, Claesson MH, Kirkin AF, Dzhandzhugazyan KN, Rosenberg J. Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study. J Exp Clin Cancer Res. 2006;25:201–6.PubMedGoogle Scholar
  68. 68.
    Lesterhuis WJ, de Vries IJM, Schuurhuis DH, et al. Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests. Ann Oncol. 2006;17:974–80.CrossRefPubMedGoogle Scholar
  69. 69.
    Lou E, Marshall J, Aklilu M, Cole D, Chang D, Morse M. A phase II study of active immunotherapy with PANVAC or autologous, cultured dendritic cells infected with PANVAC after complete resection of hepatic metastases of colorectal carcinoma. Clin Colorectal Cancer. 2006;5:368–71.CrossRefPubMedGoogle Scholar
  70. 70.
    Osada T, Clay T, Hobeika A, Lyerly HK, Morse MA. NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity. Cancer Immunol Immunother. 2006;55:1122–31.CrossRefPubMedGoogle Scholar
  71. 71.
    Kavanagh B, Ko A, Venook A, et al. Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides. J Immunother. 2007;30:762–72.CrossRefPubMedGoogle Scholar
  72. 72.
    Tamir A, Basagila E, Kagahzian A, et al. Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother. 2007;56:2003–16.CrossRefPubMedGoogle Scholar
  73. 73.
    Burgdorf SK, Fischer A, Myschetzky PS, et al. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine. Oncol Rep. 2008;20:1305–11.PubMedGoogle Scholar
  74. 74.
    Tanaka F, Haraguchi N, Isikawa K, Inoue H, Mori M. Potential role of dendritic cell vaccination with MAGE peptides in gastrointestinal carcinomas. Oncol Rep. 2008;20:1111–6.PubMedGoogle Scholar
  75. 75.
    Burgdorf SK, Claesson MH, Nielsen HJ, Rosenberg J. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination. Acta Oncol. 2009;48:1157–64.CrossRefPubMedGoogle Scholar
  76. 76.
    Barth RJ, Fisher DA, Wallace PK, et al. A randomized trial of ex vivo CD40L activation of a dendritic cell vaccine in colorectal cancer patients: tumor-specific immune responses are associated with improved survival. Clin Cancer Res. 2010;16:5548–56.CrossRefPubMedGoogle Scholar
  77. 77.
    Lesterhuis WJ, de Vries IJM, Aarntzen EA, et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br J Cancer. 2010;103:1415–21.CrossRefPubMedGoogle Scholar
  78. 78.
    Lesterhuis WJ, De Vries IJM, Schreibelt G, et al. Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients. Anticancer Res. 2010;30:5091–7.PubMedGoogle Scholar
  79. 79.
    Sakakibara M, Kanto T, Hayakawa M, et al. Comprehensive immunological analyses of colorectal cancer patients in the phase I/II study of quickly matured dendritic cell vaccine pulsed with carcinoembryonic antigen peptide. Cancer Immunol Immunother. 2011;60:1565–75.CrossRefPubMedGoogle Scholar
  80. 80.
    Morse MA, Niedzwiecki D, Marshall JL, et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg. 2013. doi: 10.1097/SLA.0b013e318292919e.PubMedGoogle Scholar
  81. 81.
    Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767–811.CrossRefPubMedGoogle Scholar
  82. 82.
    Hörig H, Lee DS, Conkright W, et al. Phase I clinical trial of a recombinant canarypoxvirus (ALVAC) vaccine expressing human carcinoembryonic antigen and the B7.1 co-stimulatory molecule. Cancer Immunol Immunother. 2000;49:504–14.CrossRefPubMedGoogle Scholar
  83. 83.
    Harrop R, Connolly N, Redchenko I, 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;12:3416–24.CrossRefPubMedGoogle Scholar
  84. 84.
    Marshall JL, Hawkins MJ, Tsang KY, et al. Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen. J Clin Oncol. 1999;17:332–7.PubMedGoogle Scholar
  85. 85.
    von Mehren M, Arlen P, Tsang KY, et al. Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas. Clin Cancer Res. 2000;6:2219–28.Google Scholar
  86. 86.
    Zhu MZ, Marshall J, Cole D, Schlom J, Tsang KY. Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine. Clin Cancer Res. 2000;6:24–33.PubMedGoogle Scholar
  87. 87.
    Marshall JL, Hoyer RJ, Toomey MA, et al. Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol. 2000;18:3964–73.PubMedGoogle Scholar
  88. 88.
    Ullenhag GJ, Frödin J-E, Mosolits S, et al. Immunization of colorectal carcinoma patients with a recombinant canarypox virus expressing the tumor antigen Ep-CAM/KSA (ALVAC-KSA) and granulocyte macrophage colony- stimulating factor induced a tumor-specific cellular immune response. Clin Cancer Res. 2003;9:2447–56.PubMedGoogle Scholar
  89. 89.
    van der Burg SH, Menon AG, Redeker A, et al. Induction of p53-specific immune responses in colorectal cancer patients receiving a recombinant ALVAC-p53 candidate vaccine. Clin Cancer Res. 2002;8:1019–27.PubMedGoogle Scholar
  90. 90.
    Menon AG, Kuppen PJK, van der Burg SH, et al. Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients. Cancer Gene Ther. 2003;10:509–17.CrossRefPubMedGoogle Scholar
  91. 91.
    Harrop R, Drury N, Shingler W, et al. Vaccination of colorectal cancer patients with modified vaccinia Ankara encoding the tumor antigen 5T4 (TroVax) given alongside chemotherapy induces potent immune responses. Clin Cancer Res. 2007;13:4487–94.CrossRefPubMedGoogle Scholar
  92. 92.
    Elkord E, Dangoor A, Burt DJ, et al. Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4). Cancer Immunol Immunother. 2009;58:1657–67.CrossRefPubMedGoogle Scholar
  93. 93.
    Elkord E, Dangoor A, Drury NL, et al. An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases. J Immunother. 2008;31:820–9.CrossRefPubMedGoogle Scholar
  94. 94.
    Kaufman HL, Lenz H-J, Marshall J, et al. Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clin Cancer Res. 2008;14:4843–9.CrossRefPubMedGoogle Scholar
  95. 95.
    Marshall JL, Gulley JL, Arlen PM, et al. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol. 2005;23:720–31.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Vanessa Deschoolmeester
    • 1
    Email author
  • Evelien Smits
    • 1
    • 2
  • Marc Peeters
    • 1
    • 3
  • Jan B. Vermorken
    • 3
  1. 1.Laboratory of Cancer Research and Clinical Oncology, Center for Oncological Research AntwerpUniversity of AntwerpWilrijkBelgium
  2. 2.Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease InstituteUniversity of AntwerpWilrijkBelgium
  3. 3.Department of OncologyAntwerp University HospitalEdegemBelgium

Personalised recommendations