American Journal of Cancer

, Volume 3, Issue 5, pp 299–316 | Cite as

therapeutic vaccines for colorectal cancer

A review of clinical data
  • Philip M. Arlen
  • James L. Gulley
Review Article


A number of cancer vaccine strategies for the treatment of colorectal cancer have entered clinical trials. Whole tumor cell vaccines have been developed from both patients’ autologous tumor cells as well as established allogeneic tumor cell lines. A vaccine consisting of autologous tumor cells along with bacillus Calmette-Guerin (BCG) has shown a potential clinical benefit in patients with stage II colon cancer. Other approaches using autologous tumor cells have involved transfection of primary tumor cells with cytokine genes. Allogeneic tumor cell vaccines have also been modified to express cytokine genes.

Vectors have been studied extensively as a means of vaccine strategy. One tumor-associated antigen (TAA) that has been extensively studied in viral vector vaccines is carcinoembryonic antigen (CEA). A recombinant vaccinia virus containing the CEA transgene (rV-CEA) has been shown to elicit CEA-specific immune responses in advanced carcinoma patients. However, patients receiving multiple vaccinations had limited increases in CEA-specific responses by the third vaccination. This problem may be overcome by the use of non-replicating poxviruses, which have been shown in clinical trials to be safe and to elicit CEA-specific responses. However, recent clinical studies have shown that the optimal use of poxviruses is to prime with vaccinia, followed by boosts with avipox vectors. A recent randomized clinical trial showed that patients primed with rV-CEA and boosted with avipox-CEA had greater immune responses compared with patients receiving three 1-monthly avipox-CEA vaccinations followed by an rV-CEA vaccination. Furthermore, a statistically significant survival advantage was noted in the prime/boost arm. Ongoing studies are now incorporating the genes for costimulatory molecules along with TAA in these vectors.

Another vaccine strategy involving TAA that is currently in clinical trials for colorectal cancer is the peptide vaccine. Dendritic cells (DCs) are considered to be the most potent antigen-presenting cell, thus providing an attractive modality for cancer vaccines. In addition to using DCs for peptide-based vaccines, a number of other strategies, including transfection with messenger RNA, have produced specific T-cell responses in clinical trials. In addition, several clinical trials using murine anti-idiotype antibodies as vaccines for patients with advanced colorectal cancer have shown both immunologic responses as well as clinical responses.


Major Histocompatibility Complex Human Leukocyte Antigen Major Histocompatibility Complex Class Costimulatory Molecule Advanced Colorectal Cancer 
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.



The authors thank Debra Weingarten for her editorial assistance in the preparation of this manuscript. No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    American Cancer Society. Cancer facts and figures: 2001. A lanta (GA): American Cancer Society, 2001Google Scholar
  2. 2.
    Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2000; 343: 905–14PubMedGoogle Scholar
  3. 3.
    Fuchs EJ, Matzinger P. Is cancer dangerous to the immune system? Semin Immunol 1996; 8: 271–80PubMedGoogle Scholar
  4. 4.
    Davis ID, Jefford M, Parente P, et al. Rational approaches to human cancer immunotherapy. J Leukoc Biol 2003 Jan; 73(1): 3–29PubMedGoogle Scholar
  5. 5.
    Smyth JM, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol 2001; 2: 293–9PubMedGoogle Scholar
  6. 6.
    Vermerken 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: 345–50Google Scholar
  7. 7.
    HooverJr 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: 390–9PubMedGoogle Scholar
  8. 8.
    Harris JE, Ryan L, Hoover Jr HC, et al. Adjuvant active specific immunotherapy of stage II and III colon cancer with an autologous tumor cell vaccine: ECOG study E5283. J Clin Oncol 2000; 18: 148–57PubMedGoogle Scholar
  9. 9.
    Calmette A. Preventive vaccination against tuberculosis with BCG. Proc R Soc Med 1931; 24: 85–94Google Scholar
  10. 10.
    BastJr RC, Zbar B, Borsos T, et al. BCG and cancer (first of two parts). N Engl J Med 1974 Jun 20; 290(25): 1413–20PubMedGoogle Scholar
  11. 11.
    Wittig B, Märten A, Dorbic T, et al. Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial. Hum Gene Ther 2001; 12(3): 267–78PubMedGoogle Scholar
  12. 12.
    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 Jun; 8(5): 389–401PubMedGoogle Scholar
  13. 13.
    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: 332–7PubMedGoogle Scholar
  14. 14.
    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(23): 3964–73PubMedGoogle Scholar
  15. 15.
    Nair SK, Hull S, Coleman D. Induction of carcinoembryonic antigen (CEA)-specific cytotoxic T-lymphocyte responses in vitro using autologous dendritic cells loaded with CEA peptide or CEA RNA in patients with metastatic malignancies expressing CEA. Int J Cancer 1999; 82: 121–4PubMedGoogle Scholar
  16. 16.
    von Mehren M, Arlen P, Gulley J, et al. The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma. Clin Cancer Res 2001; 7: 1181–91Google Scholar
  17. 17.
    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: 1331–8PubMedGoogle Scholar
  18. 18.
    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: 8809–14PubMedGoogle Scholar
  19. 19.
    Fagerberg J, Steinitz M, Wigzell H, et al. Human anti-idiotypic antibodies induced a humoral and cellular immune response against a colorectal carcinoma- associated antigen in patients. Proc Natl Acad Sci USA 1995; 92: 4773–7PubMedGoogle Scholar
  20. 20.
    Denton GW, Durrant LG, Hardcastle JD, et al. Clinical outcome of colorectal cancer patients treated with human monoclonal anti-idiotypic antibody. Int J Cancer 1994; 57: 10–4PubMedGoogle Scholar
  21. 21.
    Maxwell-Armstrong CA, Durrant LG, Buckley TJ, et al. Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer. Br J Cancer 2001 Jun 1; 84(11): 1443–6PubMedGoogle Scholar
  22. 22.
    Pervin S, Chakraborty M, Bhattacharya-Chatterjee M, et al. Induction of antitumor immunity by an anti-idiotype antibody mimicking carcinoembryonic antigen. Cancer Res 1997; 57: 728–34PubMedGoogle Scholar
  23. 23.
    Ruffini PA, Kwak LW. Immunotherapy of multiple myeloma. Semin Hematol 2001; 38: 260–7PubMedGoogle Scholar
  24. 24.
    Esserman LJ, Lopez T, Montes R, et al. Vaccination with the extracellular domain of p185neu prevents mammary tumor development in neu transgenic mice. Cancer Immunol Immunother 1999; 47: 337–42PubMedGoogle Scholar
  25. 25.
    Gansbacher B, Zier K, Cronin K, et al. Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells. Blood 1992 Dec 1; 80(11): 2817–25PubMedGoogle Scholar
  26. 26.
    McBride WH, Thacker JD, Comora S, et al. Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity. Cancer Res 1992 Jul 15; 52(14): 3931–7PubMedGoogle Scholar
  27. 27.
    Schadendorf D, Czarnetzki BM, Wittig B. Interleukin-7, interleukin-12, and GM-CSF gene transfer in patients with metastatic melanoma. J Mol Med 1995 Sep; 73(9): 473–7PubMedGoogle Scholar
  28. 28.
    Finke S, Trojaneck B, Moller P. Increase of cytotoxic sensitivity of primary human melanoma cells transfected with the interleukin-7 gene to autologous and allogeneic immunologic effector cells. Cancer Gene Ther 1997 Jul–Aug; 4(4): 260–8PubMedGoogle Scholar
  29. 29.
    Hobeika AC, Clay TM, Mosca PJ, et al. Quantitating therapeutically relevant T-cell responses to cancer vaccines. Crit Rev Immunol 2001; 21: 287–97PubMedGoogle Scholar
  30. 30.
    Hodge JW, Abrams S, Schlom J, et al. Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res 1994; 54: 5552–5PubMedGoogle Scholar
  31. 31.
    Jaffee EM, Hruban RH, Biedrzycki B, et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 2001; 19: 145–56PubMedGoogle Scholar
  32. 32.
    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: 1019–27PubMedGoogle Scholar
  33. 33.
    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: 2277–84PubMedGoogle Scholar
  34. 34.
    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: 155–65PubMedGoogle Scholar
  35. 35.
    Gjertsen MK, Bjørheim J, Saeterdal I, et al. Cytotoxic CD4+ and CD8+ T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation. Int J Cancer 1997; 72: 784–90PubMedGoogle Scholar
  36. 36.
    Hoon DSB, Irie RF. Current status of human melanoma vaccines: can they control malignant melanoma? BioDrugs 1997; 7: 66–84PubMedGoogle Scholar
  37. 37.
    Morton DL, Foshag LJ, Hoon DSB, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg 1992; 216: 463–82PubMedGoogle Scholar
  38. 38.
    Morton DL, Hoon DSB, Nizze JA, et al. Polyvalent melanoma vaccine improves survival of patients with metastatic melanoma. Ann N Y Acad Sci 1993; 690: 120–34PubMedGoogle Scholar
  39. 39.
    Takahashi T, Johnson TD, Nishinaka Y, et al. IgM anti-ganglioside antibodies induced by melanoma cell vaccine correlate with survival of melanoma patients. J Invest Dermatol 1999; 112: 101–5Google Scholar
  40. 40.
    Hoon DSB, Morisaki T, Uchiyama A, et al. Augmentation of T-cell response with a melanoma cell vaccine expressing specific HLA-A antigens. Ann N Y Acad Sci 1993; 690: 343–5PubMedGoogle Scholar
  41. 41.
    Hsueh EC, Famatiga E, Gupta RK, et al. Enhancement of complement-dependent cytotoxicity by polyvalent melanoma cell vaccine (CancerVax): correlation with survival. Ann Surg Oncol 1998; 5: 595–602PubMedGoogle Scholar
  42. 42.
    Barth A, Hoon DSB, Foshag LJ, et al. Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in-vitro cellular immune response. Cancer Res 1994; 54: 3342–5PubMedGoogle Scholar
  43. 43.
    Jones RC, Kelley M, Gupta RK, et al. Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: an immunologic survival model. Ann Surg Oncol 1996; 3: 437–45PubMedGoogle Scholar
  44. 44.
    Hsueh EC, Gupta RK, Qi K, et al. TA90 immune complex predicts survival following surgery and adjuvant vaccine immunotherapy for stage IV melanoma. Cancer J Sci Am 1997; 3: 364–70PubMedGoogle Scholar
  45. 45.
    Hsueh EC, Gupta RK, Morton DL. Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine. J Clin Oncol 1998; 16: 2913–20PubMedGoogle Scholar
  46. 46.
    Wallack MK, Sivanandham M, Balch CM, et al. Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial. J Am Coll Surg 1998; 187: 69–77PubMedGoogle Scholar
  47. 47.
    Hellstrom I, Hellstrom KE, Shepard TH. Cell-mediated immunity against antigens common to human colonic carcinomas and fetal gut epithelium. Int J Cancer 1970; 6: 346–51PubMedGoogle Scholar
  48. 48.
    Elias EG, Elias LL, Didolkar MS, et al. Cellular immunity in patients with colorectal adenocarcinoma measured by autologous leukocyte migration inhibition. Cancer 1977 Aug; 40(2): 687–92PubMedGoogle Scholar
  49. 49.
    Hollinshead A, Elias EG, Arlen M, et al. Specific active immunotherapy in patients with adenocarcinoma of the colon utilizing TAAs: a phase I clinical trial. Cancer 1985 Aug 1; 56(3): 480–9PubMedGoogle Scholar
  50. 50.
    Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc Natl Acad Sci U S A 1996; 93: 11341–8PubMedGoogle Scholar
  51. 51.
    Paoletti E. Applications of pox virus vectors to vaccination: an update. Proc Natl Acad Sci U S A 1996; 93: 11349–53PubMedGoogle Scholar
  52. 52.
    Carroll MW, Moss B. Poxviruses as expression vectors. Curr Opin Biotechnol 1997; 8: 573–7PubMedGoogle Scholar
  53. 53.
    Rolph MS, Ramshaw LA. Recombinant viruses as vaccines and immunological tools. Curr Opin Immunol 1997; 9: 517–24PubMedGoogle Scholar
  54. 54.
    Weiskirch LM, Paterson Y. Listeria monocytogenes: a potent vaccine vector for neoplastic and infectious disease. Immunol Rev 1997; 158: 159–69PubMedGoogle Scholar
  55. 55.
    Kaufmann SH, Hess J. Impact of intracellular location of and antigen display by intracellular bacteria: implications for vaccine development. Immunol Lett 1999; 65: 81–4PubMedGoogle Scholar
  56. 56.
    Fenner F, Henderson DA, Arita I, et al. Smallpox and its eradication. Geneva: World Health Organization, 1988Google Scholar
  57. 57.
    Juillard V, Villefroy P, Godfrin D, et al. Long-term humoral and cellular immunity induced by a single immunization with replication-defective adenovirus recombinant vector. Eur J Immunol 1995; 25: 3467–73PubMedGoogle Scholar
  58. 58.
    Chen PW, Wang M, Bronte V, et al. Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen. J Immunol 1996; 156: 224–31PubMedGoogle Scholar
  59. 59.
    Xiang ZQ, Yang Y, Wilson JM, et al. A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier. Virology 1996; 219: 220–7PubMedGoogle Scholar
  60. 60.
    Rosenberg SA, Zhai Y, Yang JC, et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. J Natl Cancer Inst 1998; 90: 1894–900PubMedGoogle Scholar
  61. 61.
    Irvine K, et al. Comparison of a CEA-recombinant vaccinia virus, purified CEA, and an anti-idiotype antibody bearing the image of a CEA epitope in the treatment and prevention of CEA-expressing tumors. Vaccine Res 1993; 2: 79–94Google Scholar
  62. 62.
    Kass E, Schlom J, Thompson J, et al. Induction of protective host immunity to carcinoembryonic antigen (CEA), a self-antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus. Cancer Res 1999; 59: 676–83PubMedGoogle Scholar
  63. 63.
    Bernards R, Destree A, McKenzie S, et al. Effective tumor immunotherapy directed against an oncogene-encoded product using a vaccinia virus vector. Proc Natl Acad Sci U S A 1987; 19: 6854–8Google Scholar
  64. 64.
    Tsang KY, Zaremba S, Nieroda CA, et al. Generation of human eytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 1995; 87: 982–90PubMedGoogle Scholar
  65. 65.
    Cole DJ, Wilson MC, Baron PL, et al. Phase I study of recombinant CEA vaccinia virus vaccine with post vaccination CEA peptide challenge. Hum Gene Ther 1996 Jul 10; 7(11): 1381–94PubMedGoogle Scholar
  66. 66.
    Zhu MZ, Marshall J, Cole D, et al. Specific cytolytic T-ceii responses to human CEA from patients immunized with recombinant avipox-CEA vaccine. Clin Cancer Res 2000; 6: 24–33PubMedGoogle Scholar
  67. 67.
    Restifo NP, Rosenberg SA. Developing recombinant and synthetic vaccines for the treatment of melanoma. Curr Opin Oncol 1999; 11: 50–7PubMedGoogle Scholar
  68. 68.
    Bei R, Kantor J, Kashmiri SV, et al. Enhanced immune responses and anti-tumor activity by baculovirus recombinant carcinoembryonic antigen (CEA) in mice primed with the recombinant vaccinia CEA. J Immunother Emphasis Tumor Immunol 1994; 16: 275–82PubMedGoogle Scholar
  69. 69.
    Hodge JW, McLaughlin JP, Kantor JA, et al. Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses. Vaccine 1997; 15: 759–68PubMedGoogle Scholar
  70. 70.
    Irvine KR, Chamberlain RS, Shulman EP, et al. Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors. J Natl Cancer Inst 1997; 89: 1595–601PubMedGoogle Scholar
  71. 71.
    Murata K, Garcia-Sastre A, Tsuji M, et al. Characterization of in vivo primary and secondary CD8+ T cell responses induced by recombinant influenza and vaccinia viruses. Cell Immunol 1996; 173: 96–107PubMedGoogle Scholar
  72. 72.
    Bednarek MA, Sauma SY, Gammon MC, et al. The minimum peptide epitope from the influenza virus matrix protein: extra and intracellular loading of HLA-A2. J Immunol 1991; 147(12): 4047–53PubMedGoogle Scholar
  73. 73.
    Slack R, Ley L, Chang P, et al. Association between CEA-specific T cell responses (TCR) following treatment with vaccinia-CEA (V) and Alvac-CEA (A) and survival in patients (pts) with CEA-bearing cancers [abstract no. 1086]. 37th Annual Meeting of the American Society of Clinical Oncology; 2001 May 12–15; San FranciscoGoogle Scholar
  74. 74.
    Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 1992; 71: 1065–8PubMedGoogle Scholar
  75. 75.
    Chen L, Ashe S, Brady WA, et al. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 1992; 71: 1093–102PubMedGoogle Scholar
  76. 76.
    Freeman GJ, Freedman AS, Segil JM, et al. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol 1989; 143: 2714–22PubMedGoogle Scholar
  77. 77.
    Freeman GJ, Gray GS, Gimmi CD, et al. Structure, expression, and T cell costimulatory activity of the murine homologue of the human B lymphocyte activation antigen B7. J Exp Med 1991; 174: 625–31PubMedGoogle Scholar
  78. 78.
    Hellstrom KE, Hellstrom I, Linsley P, et al. On the role of costimulation in tumor immunity. Ann N Y Acad Sci 1993; 690: 225–30PubMedGoogle Scholar
  79. 79.
    Hellstrom I, Hellstrom KE. Tumor immunology: an overview. Ann N Y Acad Sci 1993; 690: 24–31PubMedGoogle Scholar
  80. 80.
    Gregory CD, Murray RJ, Edwards CE, et al. Down-regulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt’s lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med 1988; 167: 1811–24PubMedGoogle Scholar
  81. 81.
    Damle NK, Klussman K, Linsley PS, et al. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigenprimed CD4+ T lymphocytes. J Immunol 1992; 148: 1985–92PubMedGoogle Scholar
  82. 82.
    Townsend SE, Allison JP. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 1993; 259: 368–70PubMedGoogle Scholar
  83. 83.
    Chen L, Linsley PS, Hellstrom KE. Costimulation of T cells for tumor immunity. Immunol Today 1993; 14: 483–6PubMedGoogle Scholar
  84. 84.
    von Mehren M, Arlen P, Tsang KY, et al. Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas. Clin Cancer Res 2000; 6: 2219–28Google Scholar
  85. 85.
    Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425–34PubMedGoogle Scholar
  86. 86.
    Lorenz MG, Kantor JA, Schlom J, et al. Induction of anti-tumor immunity elicited by tumor cells expressing a murine LFA-3 analog via a recombinant vaccinia virus. Hum Gene Ther 1999; 10: 623–31PubMedGoogle Scholar
  87. 87.
    Uzendoski K, Kantor JA, Abrams SI, et al. Construction and characterization of a recombinant vaccinia virus expressing murine intercellular adhesion molecule-1: induction and potentiation of antitumor responses. Hum Gene Ther 1997; 8: 851–60PubMedGoogle Scholar
  88. 88.
    Grosenbach DW, Barrientos JC, Schlom J, et al. Synergy of vaccine strategies to amplify antigen-specific immune responses and anti-tumor effects. Cancer Res 2001; 61: 4497–505PubMedGoogle Scholar
  89. 89.
    Hodge JW, Sabzevari H, Yafal AG, et al. A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res 1999; 59: 5800–7PubMedGoogle Scholar
  90. 90.
    Marshall JL, Rizvi N, Fox E, et al. A Phase I study of sequential vaccinations with fowlpox-CEA (6D)-TRICOM (B7/ICAM/LFA3) alone, and in combination with vaccinia-CEA (6D)-TRICOM and GM-CSF in patients with CEA expressing carcinomas [abstract]. EORT/AACR Meeting; 2001 Oct 29–Nov 2; MiamiGoogle Scholar
  91. 91.
    Gulley J, Chen AP, Dahut W, et al. A Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer. Prostate 2002; 53: 109–17PubMedGoogle Scholar
  92. 92.
    Abrams SI, Khleif SN, Bergmann-Leitner ES, et al. Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations. Cell Immunol 1997; 182: 137–51PubMedGoogle Scholar
  93. 93.
    Gjertsen MK, Bakka A, Breivik J, et al. Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. Int J Cancer 1996; 65: 450–3PubMedGoogle Scholar
  94. 94.
    Disis ML, Grabstein KH, Sleath PR, et al. Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. Clin Cancer Res 1999; 5: 1289–97PubMedGoogle Scholar
  95. 95.
    Zaremba S, Barzaga E, Zhu M, et al. Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen. J Natl Cancer Inst 1997; 57: 4570–7Google Scholar
  96. 96.
    Goydos JS, Elder E, Whiteside TL, et al. A phase I trial of a synthetic mucin peptide vaccine: induction of specific immune reactivity in patients with adenocarcinoma. J Surg Res 1996; 63: 298–304PubMedGoogle Scholar
  97. 97.
    Finn OJ, Jerome KR, Henderson RA, et al. MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev 1995; 145: 61–89PubMedGoogle Scholar
  98. 98.
    Dudley ME, Ngo LT, Westwood J, et al. T-cell clones from melanoma patients immunized against an anchor-modified gp100 peptide display discordant effector phenotypes. Cancer J 2000; Mar–Apr; 6(2): 69–77PubMedGoogle Scholar
  99. 99.
    van Driel WJ, Kenter GG, Fleuren GJ, et al. Immunotherapeutic strategies for cervical squamous carcinoma. Hematol Oncol Clin North Am 1999; 13: 259–73PubMedGoogle Scholar
  100. 100.
    Marchand M, van Baren N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA- A1. Int J Cancer 1999; 80: 219–30PubMedGoogle Scholar
  101. 101.
    Jager E, Ringhoffer M, Dienes HP, et al. Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 1996; 67: 54–62PubMedGoogle Scholar
  102. 102.
    Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 1998; 4: 321–7PubMedGoogle Scholar
  103. 103.
    Salgaller ML, Marincola FM, Cormier JN, et al. Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides. Cancer Res 1996; 56: 4749–57PubMedGoogle Scholar
  104. 104.
    Murphy GP, Elgamal AA, Su SL, et al. Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer 1998; 83: 2259–69PubMedGoogle Scholar
  105. 105.
    Murphy GP, Tjoa BA, Simmons SJ, et al. Infusion of dendritic cells pulsed with HLA-A2-specific prostate- specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease. Prostate 1999; 38: 73–8PubMedGoogle Scholar
  106. 106.
    Jerne NK. Towards a network theory of the immune system. Ann Immunol (Paris) 1974; 125: 373–89Google Scholar
  107. 107.
    Cerny J, Hiemaux J. Concept of idiotypic network: description and functions. In: Cerny J, Hiernaux J, editors. Idiotypic network and diseases. Washington,DC: American Society for Microbiology, 1990: 12–30Google Scholar
  108. 108.
    Chakraborty M, Mukerjee S, Foon K, et al. Induction of human breast cancer-specific antibody responses in cynomolgous monkeys by a murine monoclonal anti-idiotype antibody. Cancer Res 1995; 55: 1525–30PubMedGoogle Scholar
  109. 109.
    Chatterjee M, Foon K, Köhler H. Idiotypic antibody immunotherapy of cancer. Cancer Immunol Immunother 1994; 38: 75–82PubMedGoogle Scholar
  110. 110.
    Jefferis R. What is an idiotype? Immunol Today 1993; 14: 119–21PubMedGoogle Scholar
  111. 111.
    Varela F, Coutinho A. second generation immune networks. Immunol Today 1991; 12: 159–66PubMedGoogle Scholar
  112. 112.
    Foon K, Chakraborty M, John W, et al. Immune response to the carcinoembryonic antigen in patients treated with an anti-idiotype vaccine. J Clin Investig 1995; 96: 334–42PubMedGoogle Scholar
  113. 113.
    Foon K, Bhattacharya-Chatterjee M. Idiotype vaccines in the clinic [letter]. Nat Med 1998; 4: 870PubMedGoogle Scholar
  114. 114.
    Herlyn D, Zaloudik J, Somasundaram R, et al. Anti-idiotype vaccine in colorectal cancer patients. Hybridoma 1993; 12: 515–20PubMedGoogle Scholar
  115. 115.
    Herlyn D, Benden A, Kane M, et al. Anti-idiotype cancer vaccines: pre-clinical and clinical studies. In Vivo 1991; 5: 615–24PubMedGoogle Scholar
  116. 116.
    Herlyn D, Harris D, Zaloudik J, et al. Immunomodulatory activity of monoclonal anti-idiotypic antibody to anti-colorectal carcinoma antibody CO17-1A in animals and patients. J Immunother Emphasis Tumor Immunol 1994 May; 15(4): 303–11PubMedGoogle Scholar
  117. 117.
    Durrant LG, Maxwell-Armstrong C, Buckley D, et al. A neoadjuvant clinical trial in colorectai cancer patients of the human anti-idiotypic antibody 105AD7, which mimics CD55. Clin Cancer Res 2000 Feb; 6(2): 422–30PubMedGoogle Scholar
  118. 118.
    Maxwell-Armstrong CA, Durrant LG, Robins RA, et al. Increased activation of lymphocytes infiltrating primary colorectai cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7. Gut 1999 Oct; 45(4): 593–8PubMedGoogle Scholar
  119. 119.
    Amin S, Robins RA, Maxwell-Armstrong CA, et al. Vaccine-induced apoptosis: a novel clinical trial end point? Cancer Res 2000 Jun 15; 60(12): 3132–6PubMedGoogle Scholar
  120. 120.
    Foon KA, John WJ, Chakraborty M, et al. Clinical and immune responses in advanced colorectai cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. Clin Cancer Res 1997; 3: 1267–76PubMedGoogle Scholar
  121. 121.
    Foon KA, John WJ, Chakraborty M, et al. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. J Clin Oncol 1999; 17: 2889–95PubMedGoogle Scholar
  122. 122.
    Banchereau J, Schuler-Thurner B, Palucka AK, et al. Dendritic cells as vectors for therapy. Cell 2001; 106: 271–4PubMedGoogle Scholar
  123. 123.
    Steinman RM, Dhodapkar M. Active immunization against cancer with dendritic cells: the near future. Int J Cancer 2001; 94: 459–73PubMedGoogle Scholar
  124. 124.
    Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2: 52–8PubMedGoogle Scholar
  125. 125.
    Reichardt VL, Okada CY, Liso A, et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma: a feasibility study. Blood 1999; 93: 2411–9PubMedGoogle Scholar
  126. 126.
    Nestle FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998; 4: 328–32PubMedGoogle Scholar
  127. 127.
    Palucka K, Banchereau J. Dendritic cells: a link between innate and adaptive immunity. J Clin Immunol 1999; 19: 12–25PubMedGoogle Scholar
  128. 128.
    Timmerman JM, Levy R. Dendritic cell vaccines for cancer immunotherapy. Annu Rev Med 1999; 50: 507–29PubMedGoogle Scholar
  129. 129.
    Tanaka Y, Koido S, Chen D, et al. Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice. Clin Immunol 2001; 101: 192–200PubMedGoogle Scholar
  130. 130.
    Koido S, Tanaka Y, Chen D, et al. The kinetics of in vivo priming of CD4 and CD8 T cells by dendritic/tumor fusion cells in MUC1-transgenic mice. J Immunol 2002; 168: 2111–7PubMedGoogle Scholar
  131. 131.
    Kugler A, Stuhler G, Waiden P, et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med 2000; 6: 332–6PubMedGoogle Scholar
  132. 132.
    Eisenbach L, Bar-Haim E, El-Shami K. Antitumor vaccination using peptide based vaccines. Immunol Lett 2000; 74: 27–34PubMedGoogle Scholar
  133. 133.
    Akbari O, Panjwani N, Garcia G, et al. DNA vaccination: transfection and activation of dendritic cells as key events for immunity. J Exp Med 1999; 189: 169–78PubMedGoogle Scholar
  134. 134.
    Boczkowski D, Nair SK, Snyder D, et al. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 1996; 184: 465–72PubMedGoogle Scholar
  135. 135.
    Boczkowski D, Nair SK, Nam JH. Induction of tumor immunity and cytotoxic T lymphocyte responses using dendritic cells transfected with messenger RNA amplified from tumor cells. Cancer Res 2000; 60: 1028–34PubMedGoogle Scholar
  136. 136.
    Koido S, Kashiwaba M, Chen D, et al. Induction of antitumor immunity by vaccination of dendritic cells transfected with MUC1 RNA. J Immunol 2000; 165: 5713–9PubMedGoogle Scholar
  137. 137.
    Nair SK, Boczkowski D, Morse M, et al. Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA. Nat Biotechnol 1998; 16: 364–9PubMedGoogle Scholar
  138. 138.
    Horig 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 Nov; 49(9): 504–14PubMedGoogle Scholar
  139. 139.
    Rains N, Cannan RJ, Chen W, et al. Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer. Hepatogastroenterology 2001 Mar–Apr; 48(38): 347–51PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Laboratory of Tumor Immunology and Biology, Center for Cancer ResearchNational Cancer Institute, National Institutes of HealthBethesda, MSC 1750USA

Personalised recommendations