title: Tumour secreted grp170 chaperones full-length protein substrates and induces an adaptive anti-tumour immune response in vivo.
abstract: OBJECTIVE
  We employed a grp170-secreting tumour cell system to determine whether tumour cells engineered to secrete grp170 generate an antitumour-specific immune response. Further, we examine the possibility that secreted grp170 can bind to and co-transport out of tumour cells full-length tumour antigens that may play a role in the anti-tumour immune response.
  
  
  METHODS
  Wild type Colon-26 and Colon-26 engineered to secrete grp170 were subcutaneously inoculated into BALB/c mice. Tumour growth was monitored, and variations in immunoregulatory mechanisms were evaluated using immunohistochemistry, lymphocyte depletion, ELISpot assays, and Western blot analysis.
  
  
  RESULTS
  Immunisation of animals with grp170-secreting tumour cells results in rejection of the tumour by induction of antigen-specific, CD8-dependent immune responses. The secreted grp170 is able to deliver full-length tumour antigens to the tumour microenvironment, thus making them available for uptake by antigen presenting cells (APCs) to initiate tumour-specific immune responses.
  
  
  CONCLUSIONS
  These data parallel our studies showing that hsp110 or grp170 are able to chaperone full-length proteins, and when complexed with protein antigens and used as vaccines, these complexes elicit immune responses in vivo against the protein antigens. This cell-based approach has the potential to be utilised as a tumour-specific vaccine in tumours of various histological origins.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Hilal
authors.initials: H
authors.lastname: Arnouk
authors.forename: Evan R
authors.initials: ER
authors.lastname: Zynda
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Hylander
authors.forename: Masoud H
authors.initials: MH
authors.lastname: Manjili
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Repasky
authors.forename: John R
authors.initials: JR
authors.lastname: Subjeck
authors.forename: A
authors.initials: A
authors.lastname: Latif Kazim
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006183:H-2 Antigens / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D021382:Protein Sorting Signals / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000957:Antigens, Viral, Tumor; D006023:Glycoproteins; D006183:H-2 Antigens; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; C098410:glucose-regulated protein 170; C052646:sarcoma glycoprotein gp96 rejection antigens; D007371:Interferon-gamma; D008156:Luciferases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease