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    Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro.

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    Authors
    Scheid, Christof
    Prendiville, Joseph A
    Jayson, Gordon C
    Crowther, Derek
    Fox, Brian W
    Pettit, G R
    Stern, Peter L
    Affiliation
    Cancer Research Campaign Department of Immunology, Christie Hospital, Paterson Institute for Cancer Research, Manchester, UK.
    Issue Date
    1994-10
    
    Metadata
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    Abstract
    Bryostatin 1 is a protein kinase C activator that inhibits growth of tumour cells and activates lymphocytes in vitro, properties that have encouraged its use in phase 1 clinical studies as an anticancer agent. We investigated interleukin-2(IL-2)-induced proliferation and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMC) from cancer patients receiving Bryostatin intravenously. After Bryostatin administration both LAK generation and proliferation were enhanced when patients' PBMC were stimulated with IL-2 in vitro. However, when normal donors' PBMC were cultured in vitro in the presence Bryostatin and IL-2, LAK induction was inhibited while IL-2-driven proliferation was increased. These effects were also seen following only 2 h exposure to Bryostatin and could be elicited by conditioned medium from Bryostatin-pretreated cells. Neither IL-4 nor interferon gamma was detected in the conditioned medium. Bryostatin in vitro was found to increase expression of IL-2 receptors on CD4+, CD8+ and CD56+ cells and augment the proportion of CD8+ cells in conjunction with IL-2. We conclude that Bryostatin in combination with IL-2 in vitro enhances proliferation and IL-2 receptor expression on lymphocytes, favouring CD8+ cells while suppressing the generation of LAK activity. Intravenous administration of Bryostatin increases the potential of IL-2 to induce proliferation and LAK activity in lymphocytes which, taken together with its putative direct antitumour effect, makes Bryostatin an interesting candidate for clinical trials in combination with IL-2.
    Citation
    Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro. 1994, 39 (4):223-30 Cancer Immunol. Immunother.
    Journal
    Cancer Immunology, Immunotherapy
    URI
    http://hdl.handle.net/10541/96550
    DOI
    10.1007/BF01525985
    PubMed ID
    7954524
    Type
    Article
    Language
    en
    ISSN
    0340-7004
    ae974a485f413a2113503eed53cd6c53
    10.1007/BF01525985
    Scopus Count
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    All Christie Publications
    All Paterson Institute for Cancer Research

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