Progress in the development of a therapeutic vaccine for breast cancer.

Various human malignancies are immunogenic and recent cancer vaccine trials have demonstrated potential survival benefit. Breast cancer is immunogenic and there are several tumor associated antigens for which breast cancer vaccines have been developed. Breast cancer vaccines are designed to stimulate the immune response at various steps in the native antigen processing pathway for immunosurveillance. Human epidermal growth factor receptor 2 (HER-2/neu), mucin 1 (MUC-1), and human telomerase reverse transcriptase (hTERT) are some of the most studied antigens actively being targeted for vaccination in breast cancer patients. These vaccines are designed to elicit cytotoxic and/or helper T cell responses. Over the last several years, there has been reported progress in human clinical trials for these antigens. Cancer vaccines have repeatedly been shown to be safe with production of minimal toxicity. Recent clinical advances in the development of cancer vaccines demonstrate the potential clinical benefit that cancer vaccines hold.

[1]  K. Guthrie,et al.  Persistent immunity and survival after immunization with a HER2/neu (HER2) vaccine. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  M. Ghielmini,et al.  Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. , 2010, Journal of the National Cancer Institute.

[3]  Steven Piantadosi,et al.  Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  J. Waisman,et al.  Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Martin A. Cheever,et al.  The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research , 2009, Clinical Cancer Research.

[6]  P. Schellhammer,et al.  Integrated data from 2 randomized, double‐blind, placebo‐controlled, phase 3 trials of active cellular immunotherapy with sipuleucel‐T in advanced prostate cancer , 2009, Cancer.

[7]  J. Waisman,et al.  A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  A. Stojadinovic,et al.  The Impact of HER2/neu Expression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02 , 2009, Clinical Cancer Research.

[9]  K. Anderson.  Tumor Vaccines for Breast Cancer , 2009, Cancer investigation.

[10]  Dieter Häussinger,et al.  Sorafenib in advanced hepatocellular carcinoma. , 2008, The New England journal of medicine.

[11]  S. Steinberg,et al.  Pilot Study of Vaccination with Recombinant CEA-MUC-1-TRICOM Poxviral-Based Vaccines in Patients with Metastatic Carcinoma , 2008, Clinical Cancer Research.

[12]  B. Czerniecki,et al.  Reengineering dendritic cell‐based anti‐cancer vaccines , 2008, Immunological reviews.

[13]  E. Mittendorf,et al.  Combined Clinical Trial Results of a HER2/neu (E75) Vaccine for the Prevention of Recurrence in High-Risk Breast Cancer Patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02 , 2008, Clinical Cancer Research.

[14]  T. Gooley,et al.  Kinetics of tumor-specific T-cell response development after active immunization in patients with HER-2/neu overexpressing cancers. , 2007, Clinical immunology.

[15]  A. DeMichele,et al.  Telomerase-specific T-cell immunity in breast cancer: effect of vaccination on tumor immunosurveillance. , 2007, Cancer research.

[16]  J. Peterse,et al.  The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma , 2007, Histopathology.

[17]  B. Czerniecki,et al.  Development of vaccines for high-risk ductal carcinoma in situ of the breast. , 2007, Cancer research.

[18]  H. Nisenbaum,et al.  Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. , 2007, Cancer research.

[19]  P. Schellhammer,et al.  Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  P. Solal-Céligny,et al.  Follicular lymphoma international prognostic index , 2006, Blood.

[21]  V. Apostolopoulos,et al.  Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835] , 2006, Breast Cancer Research.

[22]  G. Hortobagyi,et al.  Mechanisms of Disease: understanding resistance to HER2-targeted therapy in human breast cancer , 2006, Nature Clinical Practice Oncology.

[23]  M. Dowsett,et al.  Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. , 2005, The New England journal of medicine.

[24]  Greg Yothers,et al.  Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. , 2005, The New England journal of medicine.

[25]  C. Shriver,et al.  Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M. Watson,et al.  Mammaglobin-based strategies for treatment of breast cancer. , 2004, Current cancer drug targets.

[27]  M. Cheever,et al.  Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein--based vaccine. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  W. Hahn,et al.  Vaccination of Cancer Patients Against Telomerase Induces Functional Antitumor CD8+ T Lymphocytes , 2004, Clinical Cancer Research.

[29]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[30]  E. Thiel,et al.  Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I/II clinical trial , 2002, Cancer Immunology, Immunotherapy.

[31]  M. Cheever,et al.  Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  M. Cheever,et al.  Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  Lyndsay N Harris,et al.  Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  R. Schreiber,et al.  IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity , 2001, Nature.

[35]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[36]  M. Christian,et al.  [New guidelines to evaluate the response to treatment in solid tumors]. , 2000, Bulletin du cancer.

[37]  L. Kanz,et al.  Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. , 2000, Blood.

[38]  P. V. van Diest,et al.  Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  S. Steinberg,et al.  Durability of Complete Responses in Patients With Metastatic Cancer Treated With High-Dose Interleukin-2. Identification of the Antigens Mediating Response , 1999 .

[40]  M. Cheever,et al.  Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[41]  M. Reddish,et al.  Anti‐MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide , 1998, International journal of cancer.

[42]  F. Marincola,et al.  Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma , 1998, Nature Medicine.

[43]  Cheever,et al.  Human HER‐2/neu protein immunization circumvents tolerance to rat neu: a vaccine strategy for ‘self’ tumour antigens , 1998, Immunology.

[44]  Robert H. Collins,et al.  Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  M. Lotze,et al.  A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. , 1996, The Journal of surgical research.

[46]  S. Gendler,et al.  The epithelial mucin, MUC1, of milk, mammary gland and other tissues. , 1995, Biochimica et biophysica acta.

[47]  C B Harley,et al.  Specific association of human telomerase activity with immortal cells and cancer. , 1994, Science.

[48]  N. Lemoine,et al.  Expression of the c-erbB-3 protein in normal human adult and fetal tissues. , 1992, Oncogene.

[49]  C. Cordon-Cardo,et al.  Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. , 1990, Oncogene.

[50]  D. Barnes,et al.  The locus of the polymorphic epithelial mucin (PEM) tumour antigen on chromosome 1q21 shows a high frequency of alteration in primary human breast tumours , 1990, International journal of cancer.

[51]  W Godolphin,et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. , 1989, Science.

[52]  Cori Bargmann,et al.  The neu oncogene encodes an epidermal growth factor receptor-related protein , 1986, Nature.

[53]  P. Seeburg,et al.  Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. , 1985, Science.

[54]  F. Burnet.  Immunological aspects of malignant disease. , 1967, Lancet.

[55]  A. Schwarer,et al.  Telomerase in cancer immunotherapy. , 2010, Biochimica et biophysica acta.

[56]  J. Winter,et al.  Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: Phase III clinical trial results. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[57]  P. Hwu,et al.  A phase III multi-institutional randomized study of immunization with the gp100: 209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[58]  I. Macpherson,et al.  Breast Cancer: Targets and Therapy , 2009 .

[59]  M. Disis,et al.  Common adjuvant breast cancer therapies do not inhibit cancer vaccine induced T cell immunity , 2008, Breast Cancer Research and Treatment.

[60]  J. Peterse,et al.  The expression pattern of MUC 1 ( EMA ) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma , 2007 .

[61]  D. McNeel,et al.  Clinical translation of peptide-based vaccine trials: the HER-2/neu model. , 2001, Critical reviews in immunology.

[62]  M. Cheever,et al.  HER-2/neu oncogenic protein: issues in vaccine development. , 1998, Critical reviews in immunology.

[63]  M. Cheever,et al.  HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. , 1997, Advances in cancer research.

[64]  W. Coley.  The Classic: The Treatment of Malignant Tumors by Repeated Inoculations of Erysipelas , 1991 .