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Int J Hyperthermia ; 26(4): 366-75, 2010.
Article in English | MEDLINE | ID: mdl-20210603

ABSTRACT

PURPOSE: 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. MATERIALS AND 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.


Subject(s)
Adaptive Immunity/immunology , Antigens, Neoplasm/metabolism , Glycoproteins/metabolism , HSP70 Heat-Shock Proteins/metabolism , Molecular Chaperones/metabolism , Neoplasms/immunology , Neoplasms/metabolism , Animals , Antigens, Neoplasm/immunology , Antigens, Viral, Tumor/metabolism , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , COS Cells , Cell Line, Tumor , Chlorocebus aethiops , Female , Glycoproteins/genetics , H-2 Antigens/metabolism , HSP70 Heat-Shock Proteins/genetics , Interferon-gamma/metabolism , Luciferases/metabolism , Lymphocyte Activation/immunology , Lymphocyte Depletion , Mice , Mice, Inbred BALB C , Molecular Chaperones/genetics , Neoplasms/pathology , Proteasome Endopeptidase Complex/metabolism , Protein Binding/immunology , Protein Sorting Signals/genetics , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes, Cytotoxic/immunology , Transfection , Viral Envelope Proteins/immunology , Viral Envelope Proteins/metabolism
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