REVIEW ARTICLE: Secreted Heat Shock Protein gp96‐Ig: An Innovative Vaccine Approach

Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA
American Journal Of Reproductive Immunology (Impact Factor: 3.32). 04/2008; 59(5):407 - 416. DOI: 10.1111/j.1600-0897.2008.00594.x

ABSTRACT Heat shock proteins (HSPs) are a large family of proteins with different molecular weights and different intracellular localizations. These proteins undertake crucial functions in maintaining cell homeostasis, and therefore they have been conserved during evolution. HSP gp96 also known as glucose-regulated protein grp94, is the primary chaperone of the endoplasmatic reticulum. Gp96/grp94, because of its peptide chaperone capacity and its ability to interact actively with professional antigen-presenting cells (APCs), is also endowed with crucial immunological functions such as natural adjuvant for priming innate and adaptive immunity. To make gp96 accessible to the immune system without biochemical purification and without cell lysis, we generated a secreted form of gp96. The immunological properties of secreted gp96 and its implications for vaccine in human cancer and infectious diseases will be discussed.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe the current advances in immunotherapy and how they can be applied to sarcoma. This review will discuss the recent literature and selected clinical trials. Evidence supporting treatment with immunotherapy alone in sarcoma will be reviewed, as will the potential incorporation of immunotherapy into treatment for sarcoma. Sarcoma, cancer of the connective tissues, frequently strikes young people, comprising a large percentage of cancer in children and young adults, but may occur at any age. Although molecularly targeted inhibitors are of great interest in treating sarcoma patients, immunotherapy is emerging as a plausible therapeutic modality because of the recent advances in other cancer types that may be translated to sarcoma. The licensing of ipilimumab and sipuleucel-T for cancer, and the remarkable success of immunotherapy for some childhood cancers, suggest a role for immunotherapy in the treatment of tumors like sarcoma. Sarcoma is a disease for which new treatments are needed. Immunotherapies have different mechanisms of action from most current therapies and could work in concert with them. Recent advances in sarcoma biology and cancer immunotherapy suggest that our knowledge of the immune system has reached the point where it can be used to augment both targeted and multimodality therapy for sarcoma.
    Current opinion in oncology 07/2013; 25(4):390-7. · 4.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the past decade, our laboratory has developed a secreted heat shock protein (HSP), chaperone gp96, cell-based vaccine that generates effective anti-tumor and anti-infectious immunity in vivo. Gp96-peptide complexes were identified as an extremely efficient stimulator of MHC I-mediated antigen cross-presentation, generating CD8 cytotoxic T-lymphocyte responses detectable in blood, spleen, gut and reproductive tract to femto-molar concentrations of antigen. These studies provided the first evidence that cell-based gp96-Ig-secreting vaccines may serve as a potent modality to induce both systemic and mucosal immunity. This approach takes advantage of the combined adjuvant and antigen delivery capacity of gp96 for the generation of cytotoxic immunity against a wide range of antigens in both anti-vial and anti-cancer vaccination. Here, we review the vaccine design that utilizes the unique property/ability of endoplasmic HSP gp96 to bind antigenic peptides and deliver them to antigen-presenting cells.
    Immunologic Research 11/2013; · 2.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inducible heat-shock protein 70 (HSP70i) is a protein regulated by stress that protects cells from undergoing apoptosis. Such proteins are marvellously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. In the presence of stress proteins, dendritic cells (DCs) will sense this alarm signal and respond by recruiting immune cells of different plumage to fit the occasion. In times of stress, melanocytes will secrete antigen-bound HSP70i to act as an alarm signal in activating DCs that comes equipped with an address of origin to drive the autoimmune response in vitiligo. Here we pose that if the autoimmune response is funnelled through HSP70i, then blocking the stress protein from activating DCs can lend new treatment opportunities for vitiligo.
    Experimental Dermatology 05/2013; · 3.58 Impact Factor