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Application of the granzyme B ELISPOT assay for monitoring cancer vaccine trials

  1. Author:
    Shaftr-Weaver, K.
    Rosenberg, S.
    Strobl, S.
    Alvord, W. G.
    Baseler, M.
    Malyguine, A.

  2. Author Address

    NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, Frederick, MD 21702 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.;Malyguine, A, NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Lab Cell Mediated Immun, Bldg 560 Room 12-79, Frederick, MD 21702 USA.;amalyguine@ncifcrf.gov
    1. Year: 2006
    2. Date: May-Jun
  2. Journal: Journal of Immunotherapy
    1. 29
    2. 3
    3. Pages: 328-335
  4. Type of Article: Article
  5. ISSN: 1524-9557
  1. Abstract:

    Granzyme B (GrB) is present in the granules of cytolytic lymphocytes and is a key mediator of cell-mediated target cell death via the gramile-mediated pathway. The release of GrB can be used as an indicator of a cytotoxic T lymphocyte response. Herein, we report that the GrB enzyme-linked immunospot assay (ELISPOT) can be used to measure ex vivo antigen-specific cytotoxicity of peripheral blood mononuclear cells from cancer patients vaccinated with a peptide-based cancer vaccine. We compare the reactivity of patients' peripheral blood mononuclear cells in the GrB ELISPOT with reactivity in the tetramer, interferon (IFN)-gamma ELISPOT, and Cr-51-release assays. Differences in immune response over all assays tested were found between patients and 4 response patterns were observed. Reactivity in the GrB ELISPOT was more closely associated with cytotoxicity in the 51Cr-release assay than the tetramer or IFN-gamma ELISPOT assays. Moreover, the higher affinity g209-2M peptide (used for vaccination) elicited greater GrB secretion than the native g209 peptide, although this difference was not observed with IFN-gamma secretion. Taken together with the fact that GrB is a specific mediator released by cytotoxic T lymphocytes, these results show that simultaneous use of the GrB ELISPOT assay with other immunologic assays may provide important additional immunologic insight into patient responses to cancer vaccines.

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External Sources

  1. View record in Web of Science®
  2. WOS: 000237328400011

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