Vaccine Therapy for Breast and Ovarian Cancers

  • Susan E. Smith
  • Alison T. Stopeck
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Breast and ovarian cancers are ideal cancer vaccine targets for several reasons. Though perhaps not as immunogenic or responsive to immunotherapies as melanoma or renal cell carcinoma, evidence of endogenous immune responses exists in many patients with breast or ovarian cancer. A number of shared antigens or potential vaccine targets also exist between these two malignancies. Both tissue and tumor-associated antigens are known and, as both organs are dispensable, breaking self-tolerance to tissue-specific antigens is feasible. Additionally, adjuvant treatment for early-stage disease in breast and ovarian cancer is common. Since it is unlikely that cancer vaccines will eradicate large tumor burdens, vaccination of patients with low tumor burden will probably be most beneficial. Patients with breast cancer are often treated in the adjuvant setting when they have no measurable disease. Ovarian cancer patients are also typically treated aggressively after presentation and can often be rendered disease-free or with minimal measurable disease. Both groups of patients also have a significant and fairly predictable rate of relapse. Patients with breast and ovarian cancer also tend to be younger, healthier, and less immunocompromised by their cancer therapies than many other cancer patients. These diseases also affect large numbers of patients. Breast cancer remains the second leading cause of cancer deaths for American women, whereas ovarian epithelial cancer ranks fifth (1). For these reasons, breast and ovarian cancers are excellent targets for cancer vaccine development with readily available patient populations for testing new vaccine approaches.


Ovarian Cancer Breast Cancer Patient Ovarian Cancer Patient Cancer Vaccine Keyhole Limpet Hemocyanin 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    North American Association for Central Cancer Registries. Data on combined rates of cancer in North America: 1994–1998.Google Scholar
  2. 2.
    Fisher ER, Gregorio RM, Fisher B. The pathology of invasive breast cancer: a syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4). Cancer 1975; 36:1–85.PubMedCrossRefGoogle Scholar
  3. 3.
    Jerome KR, Barnd DL, Bendt KM, Boyer CM, Taylor-Papadimitriou J, McKenzie IPC, et al. Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. Cancer Res 1991; 51:2908– 2916.PubMedGoogle Scholar
  4. 4.
    Kooi S, Freedman RS, Rodriguez-Villanueva, Platsoucas CD. Cytockine production by T-cell lines derived from tumor-infiltrating lymphocytes from patients with ovarian carcinoma: tumor-specific immune responses and inhibition of antigen-dependent cytokine production by ovarian tumor cells. Lymphokine Cytokine Res 1993; 12:429–437.PubMedGoogle Scholar
  5. 5.
    Melichar B, Savary C, Kudelka AP, et al. Lineage-negative human leukocyte antigen-DR+ cells the phenotype of undifferentiated dendritic cells in patients with carcinoma of the abdomen and pelvis. Clin Cancer Res 1998; 4:799–809.PubMedGoogle Scholar
  6. 6.
    Burchell J, Gendler S, Taylor-Papadimitriou J, Girling A, Lewis A, Millis R, Lamport D. Development and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of human milk mucin. Cancer Research 1987; 47:5476–5482.PubMedGoogle Scholar
  7. 7.
    Burchell J, Taylor-Papadimitriou, Griffiths AB. Strategies for the development of monoclonal antibodies for in vivo imaging: their use in the imaging of ovarian carcinoma. Cancer Detect Prey Suppl 1987; 1:241–247.Google Scholar
  8. 8.
    Bon GG, Verheijen RHM, Zuetenhorst JM, van Kamp GJ, Verstraeten AA, Kenemans. Mucin-like carcinoma-associated antigen serum levels in patients with adenocarcimonas originating from ovary, breast and colon. Gynecol Obstet Inv 1996; 42:58–62.CrossRefGoogle Scholar
  9. 9.
    Jaworek D, Zepke D, Hauber R. Technical and clinical evaluation of a new automated CA 15–3 test. In: Klapdor R, ed. Tumor associated antigens, oncogenes, receptors, cytokines in tumor diagnosis and therapy at the beginning of the nineties. Munchen: Zuckschwerdt, 1992:259–262.Google Scholar
  10. 10.
    Ioannides CG, Fisk B, Fan D, Fiddison WE, Wharton JR, O’Brian CA. Cytotoxic T cells isolated from ovarian malignant ascites recognize a peptide derived from the HER-2/neu protooncogene. Cell Immunol 1993; 151:225–234.PubMedCrossRefGoogle Scholar
  11. 11.
    Ioannides CG, Platsoucas CD, Rashed S, Wharton JT, Edwards CL, Freedman RS. Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites. Cancer Res 1991; 51:4257–4265.PubMedGoogle Scholar
  12. 12.
    Ioannides CG, Rashed S, Fisk B, Ran D, Itoh K, Freedman RS. Lymphocytes infiltrating ovarian malignant ascites: modulation of IL-2-induced proliferation by IL-4 and of selective increase in CD8+ T cells by TNF-alpha. Lymphokine Cytokine Res 1991; 10:307–315.PubMedGoogle Scholar
  13. 13.
    Ioannides CG, Fisk B, Jerome DR, Irimura T, Wharton JR, Finn OJ. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol 1993; 151: 3693–3703.PubMedGoogle Scholar
  14. 14.
    Barnd DL, Lan MS, Metzgar RS, Finn OJ. Specific major histocompatability complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells. Proc Nat Acad Sci (Wash) 1989; 86:7159–7163.CrossRefGoogle Scholar
  15. 15.
    Gourevitch MM, von Mensdorrf-Pioully S, Litvinox SV, Kenemans P, van Kamp GJ, Verstraeten AA, Hilgers J. Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients. Br J Cancer 1995; 72:934–938.PubMedCrossRefGoogle Scholar
  16. 16.
    Kotera Y, Fontenot JD, Pecher G, Metzgar RS, Finn OJ. Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients. Cancer Res 1994; 54:2856–2860.PubMedGoogle Scholar
  17. 17.
    Agrawal B, Reddish MA. Does pregnancy immunize against breast cancer? Cancer Res 1995; 55:2257.Google Scholar
  18. 18.
    Snijdewint FGM, von Mensdorff-Pouilly S, Karuntu-Wanamarta AH, Verstraeten AA, van ZantenPrzybysz I, Hummel P, Nijman HW, Kenemans P, Hilgers J. Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls. Cancer Immunol Immunother 1999; 48:47–55.PubMedCrossRefGoogle Scholar
  19. 19.
    Rilke R, Colnaghi MI, Cascinelli N, Andreola S, Baldini MT, Bufalino R, DellaPorta G, Menard S, Pierotti MA, Testori A. Prognositic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors. Int J Cancer 1991; 49:44–49.PubMedCrossRefGoogle Scholar
  20. 20.
    VonMesdorff-Pouilly S, Gourevitch MM, Kenemans P, Verstreaten AA, Litinox SV, VanKamp GJ, Paul MA, Meijer S, Vermorken J, Hilgers J. Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours. Eur J Cancer 1996; 32A:1325–1331.CrossRefGoogle Scholar
  21. 21.
    VonMesdorff-Pouilly S, Verstreaten AA, Kenemans P, Snijdewint FGM, Kok A, VanKamp GJ, Paul MA, VanDiest PJ, Meijer S, Hilgers J. Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. J Clin Oncol 2000; 18:574–583.Google Scholar
  22. 22.
    Hansen MH, Ostenstad B, Sioud M. Antigen-specific IgG antibodies in stage IV long-time survival breast cancer patients. Mol Med 2001; 7:230–239.PubMedGoogle Scholar
  23. 23.
    Hortobagyi GN, Gutterman JU, Blumenschein GR, Tashima CK, Burgess MA, Einhorn L, Buzdar AU, Richman SP, Hersh EM. Combination chemotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. Cancer 1979; 44:1955–1962.PubMedCrossRefGoogle Scholar
  24. 24.
    Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF. Chemotherapy versus chemoimmunotherapy (CAF y CAFVP y CMF each -± MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol 1987; 5:1523–1533.PubMedGoogle Scholar
  25. 25.
    Buzdar AU, Blumenschein GR, Smith TL, Powell KC, Hortobagyi GN, Yap HY, Schell FC, Barnes BC, Ames FC, Martin RG, Hersh EM. Adjuvant chemotherapy with fluorouracil, doxorubicin and cyclophosphamide, with or without bacillus Calmette-Guérin and with or without irradiation in operable breast cancer. A prospective randomized trial. Cancer 1984; 53:384–389.PubMedCrossRefGoogle Scholar
  26. 26.
    Giuliano AF, Sparks FC, Patterson K, Spears I, Morton DL. Adjuvant chemo-immunotherapy in stage II carcinoma of the breast. J Surg Oncol 1986;2 255–259.CrossRefGoogle Scholar
  27. 27.
    Hortobagyi GN, Buzdar AU, Frye D, Hug V, Fraschini G, Ames FC, Montague E, Gutterman JU, Martin RG. Combined antiestrogen and cytotoxic therapy with pseudomonas vaccine immunotherapy for metastatic breast cancer. A prospective randomized trial. Cancer 1987; 60:2596–2604.PubMedCrossRefGoogle Scholar
  28. 28.
    Aoki Y, Takakuwa K, Kodama S, Tanaka K, Takahashi M, Tokunga A, Takahashi T. Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. Cancer Res 1991; 51:1934–1939.PubMedGoogle Scholar
  29. 29.
    Freedman RS, Edwards CL, Kavanagh JJ, Kudelka AP, Katz RL, Carrasco CH, Atkinson EN, Scott W, Tomasovic B, Templin S, Platsoucas CD. Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial. J Immunother 1994; 16:198–210.CrossRefGoogle Scholar
  30. 30.
    Freedman RS, Kudelka AP, Kavanagh JJ, Verschraegen C, Edwards CL, Nash M, Levy L, Atkinson EN, Zhang EN, Melichar B, Patenia R, Templin S, Scott W, Platsoucas CD. Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 2000; 6:2268–2278.PubMedGoogle Scholar
  31. 31.
    Freedman RS, Edswards CL, Bowen JM, Lotzova E, Katz R, Lewis E, Atkinson N, Carsetti R. Viral oncolysates in patients with advanced ovarian cancer. Gynecol Oncol 1988; 29:337–347.PubMedCrossRefGoogle Scholar
  32. 32.
    Jiang XP, Yang DC, Elliot RL, Head JF. Vaccination with a mixed vaccine of autologous and allogeneic breast cancer cells and tumor associated antigens CA 15–3, CEA and CA-125-results in immune and clinical responses in breast cancer patients. Cancer Biother Radiopharm 2000; 15:495–505.PubMedCrossRefGoogle Scholar
  33. 33.
    Allred DC, Clark GM, Tandon AK, Mohn R, Tormey DC, Osborne CK, et al. HER-2/neu in nodenegative breast cancer: prognostic significance of overexpression influenced by the presence of in-situ carcinoma. J Clin Oncol 1992; 10:599–605.PubMedGoogle Scholar
  34. 34.
    Otte M, Zafrakas M, Reithdorf L,Pichlmeier U, Loning T, Janicke F, Pantel K. MAGE-A gene expression pattern in primary breast cancer. Cancer Res 2001; 61:6682–6687.PubMedGoogle Scholar
  35. 35.
    Spizzo G, Obrist P, Ensinger C, Theurl I, Dunser M, Ramoni A, Gunsilius E, Eibl G, Mikuz G, Gast G. Prognostic significance of Ep-CAM and HER-2/neu overexpression in invasive breast cancer. Int J Cancer 2002; 98:883–888.PubMedCrossRefGoogle Scholar
  36. 36.
    Agrawal B, Reddish MA, Longenecker BM. In vitro induction of MUC-1 peptide-specific Type 1 T lymphocyte and cytotoxic T lymphocyte responses from healthy multiparous donors. J Immunol 1996; 157:2089–2095.PubMedGoogle Scholar
  37. 37.
    Hinoda Y, Nakagawa N, Nakamura H, Makiguchi Y, Itoh F, Adachi M, Yanaba T, Imai K, Yachi A. Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC-1, in ulcerative colitis. Immunol (Lett) 1993; 35:163–168.CrossRefGoogle Scholar
  38. 38.
    Gileweski T, Adluri S, Ragupathi G, Zhang S, Yao T, Panageas K, Moynahan M, Houghton A, Norton L, Livingston PO. Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin Cancer Res 2000; 6:1693–1701.Google Scholar
  39. 39..
    Gileweski T, Ragupathi G, Bhuta S,.Google Scholar
  40. 40.
    Adluri S, Gilewski T, Zhang S, Ramnath V, Ragupathi G, Livingston P. Specificity analysis of sera from breast cancer patients vaccinated with MUC1-KLH plus QS-21. Br J Cancer 1999; 79:1806–1812.PubMedCrossRefGoogle Scholar
  41. 41.
    Gileweski T, Ragupathi G, Bhuta S, Clausen H, Norton L, Houghton A, Livingston P. Preliminary data: vaccination with glycolsylated mucin 1 (MUC-1)-keyhole limpet hemocyanin (KLH) conjugate plus the immunological adjuvant QS21 in breast cancer patients. Proc Am Soc Clin Oncol 2001; A1082.Google Scholar
  42. 42.
    Reddish MA, MacLean GD, Koganty RR, Kan-Mitchell J, Jones V, Mitchell MS, Longenecker BM. Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide. Int J Cancer 1998; 76:817–823.PubMedCrossRefGoogle Scholar
  43. 43.
    Goydos JS, Elder E, Whiteside TL, Finn OJ, Lotze MT. A phase I trial of a synthetic mucin peptide vaccine. J Surg Res 1996; 63:298–304.PubMedCrossRefGoogle Scholar
  44. 44.
    Karanikas V, Hwang L, Pearson J, Ong CS, Apostolopoulos V, Vaughan H, Xing PX, Jamieson G, Peitersz G, Tait B, Broadbent R, Thynne G, McKenzie IFC. Antibody and T cell responses of patients with adenocarcinoma immunized with Mannan-MUC1 fusion protein. J Clin Invest 1997; 100:2783–2792.PubMedCrossRefGoogle Scholar
  45. 45.
    Karanikas V, Thynne G, Mitchell P, Ong CS, Gunawardana D, Blum R, Pearson, J, Lodding J, Pietersz G, Broadbent R, Tait B, McKenzie IFC. Mannan mucin-1 peptide immunization: influence of cyclophophamide and the route of injection. J Immunother 2001; 24:172–183.CrossRefGoogle Scholar
  46. 46.
    Snijdewint FGM, von Mensdorff-Pouilly S, Karuntu-Wanamarta AH, Verstraeten AA, Hilgers J, Kenemans P. Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients. Int J Cancer 2001; 93:97–106.PubMedCrossRefGoogle Scholar
  47. 47.
    Musseli C, Ragupathi G, Gilewski T, Panageas KS, Spinat Y, Livingston PO. Reevaluation of the cellular immune response in breast cancer patients vaccinated with MUC 1 . Int J Cancer 2002; 97: 660–667.CrossRefGoogle Scholar
  48. 48.
    Kobayashi H, Terao T, Kawashima Y. Sialy Tn as a prognostic marker in epithelial ovarian cancer. Br J Cancer 1992; 66:984–985.PubMedCrossRefGoogle Scholar
  49. 49.
    MacLean GD, Reddish M, Koganty RR, Wong T, Gandhi S, Smolenski M, Samuel J, Nabholtz JM, Longenecker BM. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. Cancer Immunol Immunother 1993; 36:215–222.PubMedCrossRefGoogle Scholar
  50. 50.
    MacLean GD, Miles DW, Rubens RD, Reddish M, Longenecker BM. Enhancing the effect of Theratope STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J Immunother 1996; 19:309–316.CrossRefGoogle Scholar
  51. 51.
    MacLean GD, Reddish M, Koganty RR, Longenecker BM. Antibodies against mucin-associated sialylTn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother 1996; 19;58–68.Google Scholar
  52. 52.
    Holmberg LA, Oparin DV, Gooley T, Lilleby K, Bensinger W, Reddish MA, MacLean GD, Longenecker BM, Sandmaier BM. Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and Theratope STn-KLH cancer vaccine. Bone Marrow Transpl 2000; 25:1233–1241.CrossRefGoogle Scholar
  53. 53.
    Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG. Pre-existant immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. Breast Cancer Res Treat 2000; 62:245–252.PubMedCrossRefGoogle Scholar
  54. 54.
    Disis ML, Shiffman K. Cancer vaccines targeting the HER-2/neu oncogenic protein. Sem Oncol 2001; 28:12–20.CrossRefGoogle Scholar
  55. 55.
    Lohrisch C, Piccart M. An overview of HER2. Sem Oncol 2001; 28:3–11.CrossRefGoogle Scholar
  56. 56.
    Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, et al. Existent T-cell and antibody immunity to the HER-2/neu protein in patients with breast cancer. Cancer Res 1994; 54:16–20.PubMedGoogle Scholar
  57. 57.
    Disis ML, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA. High-titer HER-2/neu proteinspecific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 1997; 15:3363–3367.PubMedGoogle Scholar
  58. 58.
    Liu E, Thor A, He M, Barcos M, Ljung BM, Benz C. The HER2 (c-erb-2) oncogene is frequently amplified in in situ carcinomas of the breast. Oncogene 1992; 7:1027–1032.PubMedGoogle Scholar
  59. 59.
    Yip YL, Ward RL. Anti-ErbB-2 monoclonal antibodies and ErbB-2-directed vaccines. Cancer Immunol Immunother 2002; 50:569–587.PubMedCrossRefGoogle Scholar
  60. 60.
    Disis ML, Knutson KL, McNeel DG, Davis D, Schiffman K. Clinical translation of peptide-based vaccine trials: the HER-2/neu model. Crit Rev Immunol 2001; 21:263–273.PubMedCrossRefGoogle Scholar
  61. 61.
    Disis ML, Grabstein KH, Sleath PR, Cheever MA. 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; 5:1289–1297.PubMedGoogle Scholar
  62. 62.
    Knutson KL, Schiffman K, Disis ML. Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients. J Clin Invest 2001; 107:477–484.PubMedCrossRefGoogle Scholar
  63. 63.
    Disis ML, Shiffman K, Gooley TA, McNeel DG, Rinn K, Knutson KL. Delayed-type hypersensitivity response is a predictor of peripheral blood T-cell immunity after HER-2/neu peptide immunization. Clin Cancer Res 2000; 6:1347–1350.PubMedGoogle Scholar
  64. 64.
    Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Schiffman K. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide based vaccines. J Clin Oncol 2002; 20:2624–2632.PubMedCrossRefGoogle Scholar
  65. 65.
    Verheijen RHM, VonMesdorff-Pouilly S, VanKamp GJ, Kenemans P. CA 125: fundamental and clinical aspects. Semin Cancer Biology 1999; 9:117–124.CrossRefGoogle Scholar
  66. 66.
    Reinartz S, Boerner H, Koehler S, VonRuecker A, Schlebusch H, Wagner U. Evaluation of immunological responses in patients with ovarian cancer treated with the anti-idiotype vaccine ACA125 by determination of intracellular cytokines-a preliminary report. Hybridoma 1999; 18:41–45.PubMedCrossRefGoogle Scholar
  67. 67.
    Wagner U, Schlebusch H, Kohler S, Schmolling J, Grunn U, Krebs D. Immunological responses to the tumor-associated antigen CA 125 in patients with advanced ovarian cancer induced by the murine monoclonal anti-idiotype vaccine ACA125. Hybridoma 1997; 16:33–40.PubMedCrossRefGoogle Scholar
  68. 68.
    Old LJ, Chen YT. New paths in human cancer serology. J Exp Med 1998; 187:1163–1167.PubMedCrossRefGoogle Scholar
  69. 69.
    Jager K, Stockert E, Scanlan MJ, Gure AO, Jager E, Knuth A, Old LJ, Chen YT. Cancer-testis antigens and INGI tumor suppressor gene product are breast cancer antigens: characterization of tissue-specific ING1 transcripts and a homologue gene. Cancer Res 1999; 59:6197–6204.PubMedGoogle Scholar
  70. 70.
    Gillespie AM, Rodgers S, Wilson AP, Tidy J, Rees RC, Coleman RE, Murray AK. MAGE, BAGE and GAGE: tumor antigen expression in benign and malignant ovarian tissue. Br J Cancer 1998; 78: 816–821.PubMedCrossRefGoogle Scholar
  71. 71.
    MacLean GD, Bowen-Yacyshyn MB, Samuel J, Meikle A, Stuart G, Nation J, et al. Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenrich) determinant using a synthetic carbohydrate antigen. J Immunother 1992; 11:292–305.PubMedCrossRefGoogle Scholar
  72. 72.
    Sabbatini PJ, Kudryashov V, Ragupahti G, Danishefky SJ, Livingston PO, Bommann W, Spassova M, Zatorki A, Spriggs D, Aghahanian C, Siognet S, Peyton M, O’Flaherty C, Curtin J, Lloyd KO. Immunization of ovarian cancer patients with a synthetic lewis-protein conjugate vaccine: a phase I trial. Int J Cancer 2000; 87:79–85.PubMedCrossRefGoogle Scholar
  73. 73.
    Hui KM, Ang PT, Huang L, Tay SK. Phase I study of immunotherapy of cutaneous metastases of human carcinoma using allogenic xenogeneic MHC DNA-liposome complexes. Gene Ther 1997; 4:783–790.PubMedCrossRefGoogle Scholar
  74. 74.
    Tartour E, Mehtali M, Sastre-Garau X, Joyeux I, Mathiod C, Pleau JM, Squiban P, Rochlitz C, Courtney M, Jantscheff P, Herrman R, Pouillart P, Fridman WH, Dorval T. Phase I clinical trial with IL-2transfected xenogeneic cells administered in subcutaneous metastatic tumors: clinical and immunologic findings. Br J Cancer 2000; 83:1454–1461.PubMedCrossRefGoogle Scholar
  75. 75.
    Cowan KH, Moscow JA, Huang H, et al. Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients. Clin Can Res 1999; 5:1619–1628.Google Scholar
  76. 76.
    Hortobagyi GN, Ueno NT, Zia W, et al. Cationic liposome-mediated ElA gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial. J Clin Oncol 2001; 19:3422–3433.PubMedGoogle Scholar
  77. 77.
    Pandha HS, Martin LA, Rigg A, Hurst HC, Stamp GW, Sikora K, Lemoine NR. Genetic prodrug activation therapy for breast cancer: a phase I clinical trial of erbB-2-directed suicide gene expression. J Clin Oncol 1999; 17:2180–2189.PubMedGoogle Scholar
  78. 78.
    Yoo GH, Hung MC, Lopez-Berestein G, LaFollette S, Ensley JF, Carey M, Batson E, Reynolds TC, Murray JL. Phase I trial of intratumoral lipposome IlA gene therapy in patients with recurrent breast and head and neck cancer. Clin Can Res 2001; 7:1237–1245.Google Scholar
  79. 79.
    Cunningham CC, Holmund JT, Schiller JH, Geary RS, Twoh TJ, Don A, Nemunaitis J. A phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 adminstered as a continuous intravenous infusion in patients with advanced cancer. Clin Can Res 2000; 6:1626–1631.Google Scholar
  80. 80.
    Dummer R, Bergh J, Karlsson Y, Horowitz JA, Mulder NH, Huinink DTB, Burg G, Hofbauer G, Osanto S. Biologic activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors. Cancer Gene Ther 2000; 7:1069–1076.PubMedCrossRefGoogle Scholar
  81. 81.
    Rudin CM, Holmund J, Fleming GF, Mani S, Stadler WM, Schumm P, Monia BP, Johnston JF, Geary R, Yu RZ, Kwoh TJ, Dorr FA, Ratain MJ. Phase I trial of ISIS 5132, an antisense oligonucleotide inhibito of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. Clin Cancer Res 2001; 7:1214–1220.PubMedGoogle Scholar
  82. 82.
    Tait DL, Obermiller PS, Hatmaker AR, Redlin-Frazier S, Holt JT. Ovarian cancer BRCA1 gene therapy: phase I and II trial differences in immune response and vector stability. Clin Cancer Res 1999; 5:1708–1714.PubMedGoogle Scholar
  83. 83.
    Tait DL, Obermiller PS, Redlin-Frazier S, Jensen RA, Welcsh P, Dann J, King MC, Johnson DH, Holt JT. A phase I trial of retroviral BRCAlsv gene therapy in ovarian cancer. Clin Cancer Res 1997; 3:1959–1968.PubMedGoogle Scholar
  84. 84.
    Stopeck AT, Jones A, Hersh EM, Thompson JA, Finucane DM, Gutheil JC, Gonzalez R. Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/32-microglobulin DNA-liposome complex, in patients with metastatic melanoma. Clin Cancer Res 2001; 7:2285–2291.PubMedGoogle Scholar
  85. 85.
    Brossart P, Wirths S, Brugger W, Kanz L. Dendritic cells in cancer vaccines. Exp Hematol 2001; 29:1247–1255.PubMedCrossRefGoogle Scholar
  86. 86.
    Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W. Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 2000; 96:3102–3108.PubMedGoogle Scholar
  87. 87.
    Disis ML, Rinn K, Knutson KL, Davis D, Caron D, dela Rosa C, Schiffman K. F1t3 ligand as a vaccine adjuvant in association with HER-2/neu peptide-based vaccines in patients with HER-2/neuoverexpressing cancers. Blood 2002; 99:2845–2850.PubMedCrossRefGoogle Scholar
  88. 88.
    Hernando JJ, Park TW, Kubler K, Offergeld R, Schlebusch H, Bauknecht T. Vaccination with autologous tumor antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunologic evaluation of a phase I trial. Cancer Immunol Immunother 2002; 51:45–52.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Susan E. Smith
  • Alison T. Stopeck

There are no affiliations available

Personalised recommendations