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

2.50
Hdl Handle:
http://hdl.handle.net/10541/96550
Title:
Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro.
Authors:
Scheid, Christof; Prendiville, Joseph A; Jayson, Gordon C ( 0000-0002-8515-8944 ) ; Crowther, Derek; Fox, Brian W; Pettit, G R; Stern, Peter L
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.
Affiliation:
Cancer Research Campaign Department of Immunology, Christie Hospital, Paterson Institute for Cancer Research, Manchester, UK.
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
Issue Date:
Oct-1994
URI:
http://hdl.handle.net/10541/96550
DOI:
10.1007/BF01525985
PubMed ID:
7954524
Type:
Article
Language:
en
ISSN:
0340-7004
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorScheid, Christofen
dc.contributor.authorPrendiville, Joseph Aen
dc.contributor.authorJayson, Gordon Cen
dc.contributor.authorCrowther, Dereken
dc.contributor.authorFox, Brian Wen
dc.contributor.authorPettit, G Ren
dc.contributor.authorStern, Peter Len
dc.date.accessioned2010-04-14T11:53:39Z-
dc.date.available2010-04-14T11:53:39Z-
dc.date.issued1994-10-
dc.identifier.citationImmunomodulation 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.en
dc.identifier.issn0340-7004-
dc.identifier.pmid7954524-
dc.identifier.doi10.1007/BF01525985-
dc.identifier.urihttp://hdl.handle.net/10541/96550-
dc.description.abstractBryostatin 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.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAdjuvants, Immunologic-
dc.subject.meshAdult-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBryostatins-
dc.subject.meshCD8-Positive T-Lymphocytes-
dc.subject.meshCell Division-
dc.subject.meshCells, Cultured-
dc.subject.meshCulture Media, Conditioned-
dc.subject.meshDrug Interactions-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInfusions, Intravenous-
dc.subject.meshInterleukin-2-
dc.subject.meshKiller Cells, Lymphokine-Activated-
dc.subject.meshLactones-
dc.subject.meshLymphocyte Activation-
dc.subject.meshLymphocytes-
dc.subject.meshMacrolides-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasms-
dc.subject.meshReceptors, Interleukin-2-
dc.titleImmunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Immunology, Christie Hospital, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalCancer Immunology, Immunotherapyen

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