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

Christof Scheid, Joseph Prendiville, Gordon Jayson, Derek Crowther, Brian Fox, George Pettit, Peter L. Stern

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 γ 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.

Original languageEnglish (US)
Pages (from-to)223-230
Number of pages8
JournalCancer Immunology Immunotherapy
Volume39
Issue number4
DOIs
StatePublished - Jul 1994

Fingerprint

Bryostatins
Immunomodulation
Interleukin-2
Lymphocytes
Lymphokines
Blood Cells
Interleukin-2 Receptors
Conditioned Culture Medium
Lymphokine-Activated Killer Cells
bryostatin 1
Clinical Studies
In Vitro Techniques
Interleukin-4
Intravenous Administration
Antineoplastic Agents
Protein Kinase C
Interferons
Neoplasms
Tissue Donors
Clinical Trials

Keywords

  • Bryostatin I
  • Cancer
  • Clinical study
  • Interleukin-2
  • LAK

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

Cite this

Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study : comparison with effects of Bryostatin 1 on lymphocyte function in vitro. / Scheid, Christof; Prendiville, Joseph; Jayson, Gordon; Crowther, Derek; Fox, Brian; Pettit, George; Stern, Peter L.

In: Cancer Immunology Immunotherapy, Vol. 39, No. 4, 07.1994, p. 223-230.

Research output: Contribution to journalArticle

Scheid, Christof ; Prendiville, Joseph ; Jayson, Gordon ; Crowther, Derek ; Fox, Brian ; Pettit, George ; Stern, Peter L. / Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study : comparison with effects of Bryostatin 1 on lymphocyte function in vitro. In: Cancer Immunology Immunotherapy. 1994 ; Vol. 39, No. 4. pp. 223-230.
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