Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro
| Autor: | Brian W Fox, Gordon C Jayson, Derek Crowther, George R. Pettit, Peter L. Stern, Joseph A Prendiville, Christof Scheid |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Interleukin 2 Cancer Research Bryostatin 1 Lymphocyte medicine.medical_treatment Receptor expression Immunology Antineoplastic Agents CD8-Positive T-Lymphocytes Pharmacology Lymphocyte Activation Peripheral blood mononuclear cell Lactones chemistry.chemical_compound Adjuvants Immunologic Neoplasms medicine Humans Immunology and Allergy Drug Interactions Lymphocytes Bryostatin Infusions Intravenous Killer Cells Lymphokine-Activated Cells Cultured Lymphokine-activated killer cell business.industry Receptors Interleukin-2 hemic and immune systems Middle Aged Bryostatins medicine.anatomical_structure Cytokine Oncology chemistry Culture Media Conditioned Interleukin-2 Female Macrolides business Cell Division medicine.drug |
| Zdroj: | Cancer Immunology Immunotherapy. 39:223-230 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/bf01525985 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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