Advertisement

Gene-Modified Tumor-Cell Vaccines

  • Leisha A. Emens
  • Elizabeth M. Jaffee
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The remarkable advances in biotechnology of the late 20th century created the necessary tools for further defining the principles of tumor immunology and immunotherapy. New and more efficient gene transfer technologies have been developed to enable the expression of specific immune-activating genes at desired levels by tumor cells. The ready availability of recombinant, immune-activating cytokines and chemokines has facilitated assessment of their activity delivered either systemically as a traditional drug, or by gene transfer in preclinical models and clinical trials. Dissection of the molecular mechanisms of T-cell activation has revealed a complex network of signaling pathways that integrate the positive and negative stimuli impinging on the T cell to determine its ultimate functional status. This has created a number of targets for ex vivo and in vivo manipulation to maximize vaccine-activated antitumor immune responses.

Keywords

Renal Cell Carcinoma Major Histocompatibility Complex Major Histocompatibility Complex Class Antitumor Immunity Autologous Tumor 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Coley W. The treatment of malignant tumors by repeated inoculations of Erysipelas: with a report of ten original cases. Am J Med 1893; 105:487–511.Google Scholar
  2. 2.
    Nauts HC, Swift WE, Coley BL. The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M.D., reviewed in the light of modern research. Cancer Res 1946; 6:205–216.PubMedGoogle Scholar
  3. 3.
    Langer E. Human experimentation: cancer studies at Sloan-Kettering stir public debate on medical ethics. Science 1964; 143:551–553.PubMedGoogle Scholar
  4. 4.
    Prehn R. Immunity to Methylcholanthrene-induced sarcomas. J Natl Cancer Inst 1957; 18:769–778.PubMedGoogle Scholar
  5. 5.
    Prehn R. Stimulatory effects of immune reactions upon the growths of untransplanted tumors. Cancer Res 1994; 54:908–914.PubMedGoogle Scholar
  6. 6.
    Hoover HJ, Surdyke M, Dangel RB, et al. Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer. Cancer 1985; 55:1236–1243.PubMedGoogle Scholar
  7. 7.
    Hoover HJ, 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; 11:390–399.PubMedGoogle Scholar
  8. 8.
    Berd D, Maguire HCJ, McCue P. Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J Clin Oncol 1990; 8:1858–1867.PubMedGoogle Scholar
  9. 9.
    Lipton A, Harvey HA, Balch CM. Corynebacterium parvum versus bacille Calmette-Guérin adjuvant immunotherapy of stage II malignant melanoma. J Clin Oncol 1991; 9:1151–1156.PubMedGoogle Scholar
  10. 10.
    McCune CS, O’Donnell RW, Marquis DM. Renal cell carcinoma treated by vaccines for active specific immunotherapy: correlation of survival with skin testing by autologous tumor cell-bacille CalmetteGuérin vaccine. Cancer Immunol Immunother 1990; 32:62–66.PubMedGoogle Scholar
  11. 11.
    Lindeman J, Klein P. Viral oncolysis: increased immunogenicity of host cell antigen associated with influenza virus. J Exp Med 1967; 126:93–102.Google Scholar
  12. 12.
    Lee RE, Lotze, MT, SkibberJM. Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 1989; 7:7–20.PubMedGoogle Scholar
  13. 13.
    Hieber U, Heim ME. Tumor necrosis factor for the treatment of malignancies. Oncology 1994; 51: 142–153.PubMedGoogle Scholar
  14. 14.
    Veelken H, Rosenthal FM, Schneller F, et al. Combination of interleukin-2 and interferon-alpha in renal cell carcinoma and malignant melanoma: a phase II clinical trial. Biotech Ther 1992; 3:1–14.Google Scholar
  15. 15.
    Buzio C, Andrulli S, Santi R, et al. Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma. Cancer 2001; 92:2286–2296.PubMedGoogle Scholar
  16. 16.
    Forni G, Fujiwara H, Martino F, et al. Helper strategy in tumor immunology: expansion of helper lymphocytes and utilization of helper lymphokines for experimental and clinical immunotherapy. Cancer Met Rev 1988; 7:289–309.Google Scholar
  17. 17.
    Matzinger P. Tolerance, danger, and the extended family. Ann Rev Immunol 1994; 12:991–1045.Google Scholar
  18. 18.
    Brichard V, van Pel A, Wolfel T, et al. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1993; 178(2):489–495.PubMedGoogle Scholar
  19. 19.
    van der Bruggen P, Traverari C, Chomez P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254:1643–1647.PubMedGoogle Scholar
  20. 20.
    Cox AL, Skipper J, Chen Y, et al. Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 1994; 264(5159):716–719.PubMedGoogle Scholar
  21. 21.
    Bakker AB, Schrears MW, de Boer AJ, et al. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med 1994; 179(3):1005–1009.PubMedGoogle Scholar
  22. 22.
    Kawakami Y, Eliyahu S, Delgado CH, et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci USA 1994; 91(9):3515–3519.PubMedGoogle Scholar
  23. 23.
    Coulie PG, Brichard VP, van Pel A, et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1994; 180(1):35–42.PubMedGoogle Scholar
  24. 24.
    Huang AY, Golumbek P, Ahmadzadeh M, et al. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994; 264:961–965.PubMedGoogle Scholar
  25. 25.
    Huang AY, Bruce AT, Pardoll DM, et al. In vivo cross-priming of MHC class I-restricted antigens requires TAP transporter. Immunity 1996; 4:349–355.PubMedGoogle Scholar
  26. 26.
    Fakhrai H, Shawler DL, Van Beveren C, et al. Cytokine gene therapy with interleukin-2 transduced fibroblasts: effects of IL-2 dose on antitumor immunity. Human Gene Ther 1995; 6:591–601.Google Scholar
  27. 27.
    Borrello I, Sotomayor EM, Cooke S, et al. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. Human Gene Ther 1999; 10:1983–1991.Google Scholar
  28. 28.
    Chen CA, Okayama H. Calcium-phosphate mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques 1988; 6:882–886.Google Scholar
  29. 29.
    Kubiniec RT, Liang H, Hui SW. Effects of pulse length and pulse strength on transfection by electroporation. Biotechniques 1990; 8:16–20.PubMedGoogle Scholar
  30. 30.
    Cappechi MR. High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 1980; 22:479.Google Scholar
  31. 31.
    Felgner PL, Gadek TR, Holm M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 1980; 84:7413–7418.Google Scholar
  32. 32.
    Hu W-S, Pathak VK. Design of retroviral vectors and helper cells for gene therapy. Pharmacol Rev 2000; 52:493–511.PubMedGoogle Scholar
  33. 33.
    Burton EA, Wechuk JB, Wendell SK, et al. Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells 2001; 19:358–377.PubMedGoogle Scholar
  34. 34.
    Enger PO, Thorsen F, Lonning PE, et al. Adeno-associated viral vectors penetrate human solid tumor tissue in vivo more effectively than adenoviral vectors. Human Gene Ther 2002; 13:1115–1125.Google Scholar
  35. 35.
    Kost TA, Condreay JP. Recombinant baculoviruses as mammalian cell gene-delivery vectors. TRENDS Biotechnol 2002; 20:173–180.PubMedGoogle Scholar
  36. 36.
    Somia N, Verma IM. Gene therapy: trials and tribulations. Nature Rev Gen 2000; 1:91–99.Google Scholar
  37. 37.
    Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I restricted CTLs. Nature 1998; 392:86–89.PubMedGoogle Scholar
  38. 38.
    Pardoll DM. Spinning molecular immunology into successful immunotherapy. Nature Rev 2002; 2: 227–238.Google Scholar
  39. 39.
    Boon T, Cerrotini JC, Van den Eynde B, et al. Tumor antigens recognized by T lymphocytes. Ann Rev Immunol 1994; 53:337–365.Google Scholar
  40. 40.
    Jenkins MK, Schwartz R. Antigen presentation by chemically modified splenocytes induces antigenspecific T cell unresponsiveness in vitro and in vivo. J Exp Med 1987; 165:302–319.PubMedGoogle Scholar
  41. 41.
    Wallich R, Bulbec N, Hammerling G. Abrogation of metastatic properties of tumor cells by de nova expression of H-2K antigens following H-2 gene transfection. Nature 1985; 315:310–313.Google Scholar
  42. 42.
    Karre K, Ljunggren H, Piontek G. Selective rejection of H-2 deficient lymphoma variants suggests alternative immune defense strategy. Nature 1986; 319:675–678.PubMedGoogle Scholar
  43. 43.
    Thomas MC, Greten TF, Pardoll DM, et al. Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine. Human Gene Ther 1998; 9:835–843.Google Scholar
  44. 44.
    Toes RE, Blom RJ, van der Voort E, et al. Protective anti-tumor immunity induced by immunization with completely allogeneic tumor cells. Cancer Res 1996; 56:3782–3787.PubMedGoogle Scholar
  45. 45.
    Hu H-M, Urba WB, Fox BA. Gene-modified tumor vaccine with therapeutic potential shifts tumorspecific T cell response from a type 2 to a type 1 cytokine profile. J Immunol 1998; 161:3033–3041.PubMedGoogle Scholar
  46. 46.
    Mueller DL, Jenkins MK, Schwarz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Ann Rev Immunol 1989: 7:445–480.Google Scholar
  47. 47.
    Carreno BM, Collin M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Ann Rev Immunol 2002; 20:29–53.Google Scholar
  48. 48.
    Hathcock KS, Laslo G, Pucillo C, et al. Comparative analysis of B7–1 and B7–2 costimulatory ligands: expression and function. J Exp Med 1994; 180:631–640.PubMedGoogle Scholar
  49. 49.
    Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nature Immunol 2002; 2:116–126.Google Scholar
  50. 50.
    Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nature Immunol 2002; 3:611–618.Google Scholar
  51. 51.
    Chen L, Ashe S, Brady WA, et al. Co-stimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 1992; 71:1093–1102.PubMedGoogle Scholar
  52. 52.
    Baskar S, Ostrand-Rosenberg S, Navabi N. Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated MHC class II molecules. Proc Natl Acad Sci USA 1993; 12:5687–5695.Google Scholar
  53. 53.
    Townsend SE, Allison JP. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 1993; 259:368–370.PubMedGoogle Scholar
  54. 54.
    Yang G, Hellstrom KE, Hellstrom I, et al. Antitumor immunity elicited by tumor cells transfected with B7–2, a second ligand for CD28/CTLA-4 costimulatory molecules. J Immunol 1995; 154:2794–2800.PubMedGoogle Scholar
  55. 55.
    Schwartz R. Costimulation of T lymphocytes: the role of CD28, CTLA4, and B7/BB1 in interleukin 2 production and immunotherapy. Cell 1992; 71:1065–1068.PubMedGoogle Scholar
  56. 56.
    Huang AYC, Bruce AT, Pardoll DM, et al. Does B7–1 expression confer antigen-presenting cell capacity to tumors in vivo? J Exp Med 1996; 183:769–776.PubMedGoogle Scholar
  57. 57.
    Azuma M, Cayabyab M, Buck D, et al. Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural killer leukemia cell line. J Immunol 1992; 149:1115–1123.PubMedGoogle Scholar
  58. 58.
    Antonia SJ, Seigne J, Diaz J, et al. Phase I trial of a B7–1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin 2 in patients with metastatic renal cell carcinoma. J Urol 2002; 167:1995–2000.PubMedGoogle Scholar
  59. 59.
    Dols A, Meijer S, Hu H-M, et al. Identification of tumor-specific antibodies in patients with breast cancer vaccinated with gene-modified allogenic tumor cells. J Immunother 2003;26:163–170.PubMedGoogle Scholar
  60. 60.
    Dong C, Juedes AE, Temann UA, et al. ICOS costimulatory receptor is essential for T cell activation and function. Nature 2001; 409:97–101.PubMedGoogle Scholar
  61. 61.
    Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Med 2002; 8:793–800.PubMedGoogle Scholar
  62. 62.
    Kwon B, Lee HW, Kwon BS. New insights into the role of 4–1BB in immune responses: beyond CD8+ T cells. TRENDS Immunol 2002; 23:378–380.PubMedGoogle Scholar
  63. 63.
    Sunder-Plassman R, Richl WF, Majdic O, etal. Crosslinking of CD27 in the presence of CD28 costimulation results in T cell proliferation and cytokine production. Cellular Immunology 1995; 164:20–27.Google Scholar
  64. 64.
    Weinberg A. 1940: Targeted immunotherapy-implications for tempering autoimmunity and enhancing vaccines. TRENDS Immunol 2002; 23:102–109.Google Scholar
  65. 65.
    Morel Y, Truneh A, Sweet RW, et al. The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity. J Immunol 2001; 167:2479–2486.PubMedGoogle Scholar
  66. 66.
    Grewal IS and Flavell R. CD40 and CD154 in cell-mediated immunity. Ann Rev Immunol 1998; 16:111–135.Google Scholar
  67. 67.
    French RR, Chan C, Tutt AL, et al. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nature Med 1999; 5:548–553.PubMedGoogle Scholar
  68. 68.
    Zanelli E, Toes REM. A dual function for CD40 agonists. Nature Med 2000; 6:629–630.PubMedGoogle Scholar
  69. 69.
    Kato K, Cantwell MJ, Sharma S, et al. Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells. J Clin Invest 1998; 101:1133–1141.PubMedGoogle Scholar
  70. 70.
    Dotti G, Savoldo B, Takahashi S, et al. Adenovector-induced expression of human CD40-ligand (hCD4OL) by multiple myeloma cells: a model for immunotherapy. Exp Hematol 2001; 29:952–961.PubMedGoogle Scholar
  71. 71.
    Bashey A, Cantwell MJ, Kipps TJ. Adenovirus transduction to effect CD40 signaling improves the immune stimulatory activity of myeloma cells. Br J Hematol 2002; 118:506–513.Google Scholar
  72. 72.
    Dilloo D, Brown M, Roskrow M, et al. CD40 ligand induces an antileukemia immune response in vivo. Blood 1997; 90:1927–1933.PubMedGoogle Scholar
  73. 73.
    Kikuchi T, Crystal RG. Antitumor immunity induced by in vivo adenovirus vector-mediated expression of CD40 ligand in tumor cells. Human Gene Ther 1999; 10:1375–1387.Google Scholar
  74. 74.
    Loskog A, Bjorkland A, Brown MP, et al. Potent antitumor effects of CD154 transduced tumor cells in experimental bladder cancer. J Urol 2001; 166:1093–1097.PubMedGoogle Scholar
  75. 75.
    Wierda WG, Cantwell MJ, Woods SJ, et al. CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia. Blood 2000; 96:2917–2924.PubMedGoogle Scholar
  76. 76.
    Fearon E, Pardoll D, Itaya T. Interleukin 2 gene production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 1990; 60:397–405.PubMedGoogle Scholar
  77. 77.
    Gansbacher B, Zier K, Daniels B. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 1990; 172:1217–1225.PubMedGoogle Scholar
  78. 78.
    Bubenik J, Simova J, Jandlova T. Immunotherapy of cancer using local administration of lymphoid cells expressing IL 2 cDNA and constitutively producing IL-2. Immunology Lett 1990; 23:287–292.Google Scholar
  79. 79.
    Cavallo F, Giovarelli M, Gulino A. Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL 2 gene. J Immunol 1992; 149:3627–3634.PubMedGoogle Scholar
  80. 80.
    Bannerji R, Arroyo CD, Cordon-Cordo C. The role of IL-2 secreted from genetically modified tumor cells in the establishment of antitumor immunity. J Immunol 1994; 152:2324–2330.PubMedGoogle Scholar
  81. 81.
    Li W, Diamenstein T, Blankenstein T. Lack of tumorigenicity of interleukin 4 autocrine growing cells seems related to the anti-tumor function of interleukin 4. Mol Immunol 1990; 27:1331–1338.PubMedGoogle Scholar
  82. 82.
    Golumbek P, Lazenby A, Levitsky H. Treatment of established renal cancer by tumor cells engineered to secrete interleukin 4. Science 1991; 254:713–716.PubMedGoogle Scholar
  83. 83.
    Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993; 90:3539–3543.PubMedGoogle Scholar
  84. 84.
    Asher A, Mule J, Kasid A. Murine tumor cells transduced with the gene for tumor necrosis factor-a. J Immunol 1991; 146:3227–3232.PubMedGoogle Scholar
  85. 85.
    Blankenstein T, Qin Z, Uberla K. Tumor suppression after tumor cell-targeted tumor necrosis factor via gene transfer. J Exp Med 1991; 173:1047–1054.PubMedGoogle Scholar
  86. 86.
    Karp SE, Farber A, Salo JC. Cytokine secretion by genetically modified monimmunogenic murine fibrosarcoma. J Immunol 1993; 150:896–902.PubMedGoogle Scholar
  87. 87.
    Watanabe Y, Kuribiyashi K, Miyatake S. Exogenous expression of mouse interferon y cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. Proc Natl Acad Sci USA 1989; 86:9456–9461.PubMedGoogle Scholar
  88. 88.
    Gansbacher B, Banerji R, Daniels B. Retroviral vector-mediated y-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 1990; 50:7820–7826.PubMedGoogle Scholar
  89. 89.
    Restifo N, Speiss P, Karp S. A nonimmunogenic sarcoma transduced with the cDNA for interferon y elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capacity. J Exp Med 1992: 175:1423–1429.PubMedGoogle Scholar
  90. 90.
    Belardelli F, Ferrantini M, Proietti E, Kirkwood JM. Interferon-alpha in tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002; 13:119–134.PubMedGoogle Scholar
  91. 91.
    Nagai E, Ogawa T, Kielia T, et al. Irradiated tumor cells adenovirally engineered to secrete granulocyte/ macrophage colony stimulating factor establish antitumor immunity and eliminate pre-existing tumors in syngeneic mice. Cancer Immunol Immunother 1998; 47:72–80.PubMedGoogle Scholar
  92. 92.
    Colombo M, Ferrari G, Stoppacciaro A, et al. Granulocyte-colony stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med 1991; 173:889–896.PubMedGoogle Scholar
  93. 93.
    Wittig B, Marten 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. Human Gene Ther 2001; 12:267–278.Google Scholar
  94. 94.
    Moller P, Sun Y, Dorbic T, et al. Vaccination with IL-7-gene modified autologous melanoma cells can enhance melanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study. Br J Cancer 1998; 77:1907–1916.PubMedGoogle Scholar
  95. 95.
    Cayeux S, Richter G, Nottz G, et al. Influence of gene-modified (IL-7, IL-4, and B7) tumor cell vaccines on tumor antigen presentation. J Immunol 1997; 158:2834–2841.PubMedGoogle Scholar
  96. 96.
    Carsana M, Tragni G, Nicolini G, et al. Comparative assessment of TCRVb diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor vaccine. Cancer Gene Ther 2002; 9:243–253.PubMedGoogle Scholar
  97. 97.
    Lotze MT, Zitvogel L, Campbell R, et al. Cytokine gene therapy of cancer using interleukin-12: murine and clinical trials. Ann NY Acad Sci 1996; 795:440–454.PubMedGoogle Scholar
  98. 98.
    Sun Y, Jurgovsky K, Moller P, et al. Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 1998; 5:481–490.PubMedGoogle Scholar
  99. 99.
    Dunissi-Joannopouolos K, Runyon K, Erickson J, et al. Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity. Blood 1999: 94:4263–4273.Google Scholar
  100. 100.
    Colombo MP, Trincheri G. Interleukin 12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002; 13:155–168.PubMedGoogle Scholar
  101. 101.
    Braun SE, Chen K, Blazar BR, et al. Flt3 ligand antitumor activity in a murine breast cancer model: a comparison with granulocyte-macrophage colony-stimulating factor and a potential mechanism of action. Human Gene Ther 1999; 10:2141–2151.Google Scholar
  102. 102.
    Mach N, Gillessen S, Wilson S, et al. Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or flt3-ligand. Cancer Res 2000; 60:3239–3246.PubMedGoogle Scholar
  103. 103.
    Rodolfo M, Zilocchi C, Cappetti B, et al. Cytotoxic T lymphocyte response against non-immunoselected tumor antigens predicts the outcome of gene therapy with IL-12-transduced tumor cell vaccine. Gene Ther 1999; 6:865–872.PubMedGoogle Scholar
  104. 104.
    Martinotti A, Stoppacchiaro A, Vagliani M, et al. CD4 T cells inhibit in vivo CD8-mediated immune response against a murine colon carcinoma transduced with IL-12 genes. Eur J Immunol 1995; 25: 137–146.PubMedGoogle Scholar
  105. 105.
    Colombo MP, Modesti A, Parmiani G, et al. Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T-lymphocyte cross-talk. Cancer Res 1992; 52:4852–4857.Google Scholar
  106. 106.
    Zilocchi C, Stoppacchiaro A, Chiodoni C, et al. Interferon gamma-independent rejection of interleukin 12-transduced carcinoma cells requires CD4+ T cells and granulocyte/macrophage colony-stimulating factor. J Exp Med 1998; 188:133–143.PubMedGoogle Scholar
  107. 107.
    Rodolfo M, Melani C, Zilocchi C, et al. IgG2a induced by interleukin (IL) 12-producing tumor cell vaccines but not IgG1 induced by IL-4 vaccine is associated with the eradication of experimental metastases. Cancer Res 1998; 58:5812–5817.PubMedGoogle Scholar
  108. 108.
    Coughlin CM, Wysocka M, Kurzawa HL, et al. B7–1 and interleukin 12 synergistically induce effective antitumor immunity. Cancer Res 1995; 55:4980–4987.PubMedGoogle Scholar
  109. 109.
    Hull GW, McCurdy MA, Nasu Y, et al. Prostate cancer gene therapy: comparison of adenovirusmediated expression of interleukin 12 with interleukin 12 plus B7–1 for in situ gene therapy and genemodified, cell-based vaccines. Clin Cancer Res 2000; 6:4101–4109.PubMedGoogle Scholar
  110. 110.
    Coughlin CM, Salhaney KE, Gee MS, et al. Interleukin 12 and interleukin 18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest 1998; 101:1441–1452.PubMedGoogle Scholar
  111. 111.
    Steinman RM. The dendritic cell system and its role in immunogenicity. Ann Rev Immunol 1991; 9:271–296.Google Scholar
  112. 112.
    Maraskovsky E, Brasel K, Teepe M, et al. Dramatic increase in the numbers of functionally mature dendritic cells in flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp Med 1996; 184:1953–1961.PubMedGoogle Scholar
  113. 113.
    Pulendran B, Smith J, Caspary G, et al. Distinct dendritic cell subsets differetntially regulate the class of immune response in vivo. Proc Natl Acad Sci USA 1997; 96:1036–1041.Google Scholar
  114. 114.
    Kielian T, Nagai E, Ikubo A, et al. Granulocyte/macrophage-colony-stimulating factor released by adenovirally transduced CT26 cells leads to the local expression of macrophage inflammatory protein la and accumulation of dendritic cells at vaccination sites in vivo. Cancer Immunol Immunother 1999; 48:123–131.PubMedGoogle Scholar
  115. 115.
    Shinohara H, Yano S, Bucana C, et al. Induction of chemokine secretion and enhancement of contactdependent macrophage cytotoxicity by engineered expression of granulocyte-macrophage colonystimulating factor in human colon cancer cells. J Immunol 2000; 164:2728–2737.PubMedGoogle Scholar
  116. 116.
    Simons JW, Jaffee EM, Weber CE, et al. Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer. Cancer Res 1997; 57:1537–1546.PubMedGoogle Scholar
  117. 117.
    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(1):145–156.PubMedGoogle Scholar
  118. 118.
    Soiffer R, Lynch R, Mihm M, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent anti-tumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 1998; 95:13141–13146.PubMedGoogle Scholar
  119. 119.
    Hung KH, Lafond-Walker A, Lowenstein C, et al. The central role of CD4+ T cells in the antitumor immune response. J Exp Med 1998; 188(12):2357–2368.PubMedGoogle Scholar
  120. 120.
    Machiels J-PH, Reilly RT, Emens LA, et al. Cyclophosphamide, Doxorubicin, and Paclitaxel enhance the anti-tumor immune response of GM-CSF secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res 2001; 61:3689–3697.PubMedGoogle Scholar
  121. 121.
    Dong Z, Yoneda J, Kumar R, et al. Angiostatin-mediated suppression of cancer metastatses by primary neoplasms engineered to produce granulocyte-/macrophage colony-stimulating factor. J Exp Med 1998; 188:755–763.PubMedGoogle Scholar
  122. 122.
    Jaffee EM, Pardoll DM. Considerations for the clinical development of cytokine gene-transduced tumor cell vaccines. Methods 1997; 12(2):143–153.PubMedGoogle Scholar
  123. 123.
    Jaffee EM, Thomas MC, Huang AYC, et al. Enhanced immune priming with spatial distribution of paracrine cytokine vaccines. J Immunother 1996; 19(3):176–183.Google Scholar
  124. 124.
    Simons JW, Mikhak B, Chang JF, et al. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 1999; 59:5160–5168.PubMedGoogle Scholar
  125. 125.
    Simons JW, Small E, Nelson W, et al. Phase II trials of a GM-CSF gene-transduced prostate cancer cell line vaccine (GVAXR) demonstrate antitumor activity. Proc Am Soc Clin Oncol 2001; 20:1073.Google Scholar
  126. 126.
    Neumanitis J, Sterman D, Jablons D, et al. A phase MI study of autologous GM-CSF-modified cancer vaccines in subjects with non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2001; 20:1019.Google Scholar
  127. 127.
    Homey B, Muller A, Zlotnik A. Chemokines: agents for the immunotherapy of cancer? Nature Rev Immunol 2002; 2:175–184.Google Scholar
  128. 128.
    Vicari AP, Caux C. Chemokines in cancer. Cytokine Growth Factor Rev 2002; 13:143–154.PubMedGoogle Scholar
  129. 129.
    Sallusto F, Lenig D, Mackay DR, et al. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 1998; 187:875–883.PubMedGoogle Scholar
  130. 130.
    Sallusto F, Lenig D, Forster R, et al. Two subsets of memory T lymphocytes with distinct homing potentials. Nature 1999; 401:708–712.PubMedGoogle Scholar
  131. 131.
    Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Ann Rev Immunol 2000; 18:593–620.Google Scholar
  132. 132.
    Mule JJ, Custer M, Averbook B, et al. RANTES secretion by gene-modified tumor cells results in loss of tumorigenicity in vivo: role of immune cell subpopulations. Human Gene Ther 1996; 7:1545–1553.Google Scholar
  133. 133.
    Maric M, Liu Y. Strong cytotoxic T lymphocyte responses to a macrophage inflammatory protein-la expressing tumor: linkage between inflammation and specific immunity. Cancer Res 1999; 59:5549–5553.PubMedGoogle Scholar
  134. 134.
    Saeki H, Moore AM, Brown MJ, et al. Secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol 1999; 162:2472–2478.PubMedGoogle Scholar
  135. 135.
    Cyster J. Chemokines and the homing of dendritic cells to the T cell areas of lymphoid organs. J Exp Med 1999; 189:447–450.PubMedGoogle Scholar
  136. 136.
    Vicari AP, Ait-Yahia S, Chemin K, et al. Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms. J Immunol 2000; 165:1992–2000.PubMedGoogle Scholar
  137. 137.
    Perez-Diaz A, Speiss P, Restifo NP, et al. Intensity of the vaccine-elicited immune response determines tumor clearance. J Immunol 2002; 168:338–347.Google Scholar
  138. 138.
    Zou YR, Kottman AH, Kuroda M. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998; 393:595–599.PubMedGoogle Scholar
  139. 139.
    Ma Q, Jones D, Borghesani PR. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 1998; 95:9448–9453.PubMedGoogle Scholar
  140. 140.
    Nanki T, Lipsky P. Stromal cell-derived factor-1 is a costimulator for CD4+ T cell activation. J Immunol 2000; 164:5010–5016.PubMedGoogle Scholar
  141. 141.
    Suzuki Y, Rahman M, Mitsuya H. Diverse transcriptional response of CD4+ T cells to stromal cellderived factor (SDF)-1: cell survival promotion and priming effects of SDF-1 on CD4+ T cells. J Immunol 2001; 167:3067–3073.Google Scholar
  142. 142.
    Nomura T, Hasegawa H, Kohno M. Enhancement of antitumor immunity by tumor cells transfected with secondary lymphoid tissue chemokine, EB1–1-ligand chemokine and stromal cell-derived factor la chemokine genes. Intl J Cancer 2001; 91:597–606.Google Scholar
  143. 143.
    Dunussi-Joannopoulos K, Zuberek K, Runyon K, et al. Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor-1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses. Blood 2002; 100(5):1551–1558.PubMedGoogle Scholar
  144. 144.
    Poznansky MC, Olszak IT, Foxall R. Active movement of T cells away from a chemokine. Nature Med 2000; 6:543–548.PubMedGoogle Scholar
  145. 145.
    Cairns CM, Gordon JR, Li F, et al. Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor. J Immunol 2001; 167:57–65.PubMedGoogle Scholar
  146. 146.
    Dilloo D, Bacon K, Holden W, et al. Combined chemokine and cytokine gene transfer enhances antitumor immunity. Nature Med 1996; 2:1090–1095.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Leisha A. Emens
  • Elizabeth M. Jaffee

There are no affiliations available

Personalised recommendations