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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

  • Original Articles
  • Bryostatin 1, Clinical Study, Cancer, LAK, Interleukin-2
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

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.

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Authors and Affiliations

  1. Cancer Research Campaign Department of Immunology, Christie Hospital, Paterson Institute for Cancer Research, Wilmslow Road, M20 9BX, Manchester, UK

    Christof Scheid (C.S. is the recipient of a Mildred-Scheel Research Fellowship from the Deutsche Krebshilfe) & Peter L. Stern

  2. Department of Medical Oncology, Christie Hospital, Paterson Institute for Cancer Research, Wilmslow Road, M20 9BX, Manchester, UK

    Joseph Prendiville, Gordon Jayson & Derek Crowther

  3. Department of Experimental Chemotherapy, Christie Hospital, Paterson Institute for Cancer Research, Wilmslow Road, M20 9BX, Manchester, UK

    Joseph Prendiville & Brian Fox

  4. Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe, Arizona, USA

    George R. Pettit

Authors
  1. Christof Scheid
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  2. Joseph Prendiville
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  3. Gordon Jayson
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  4. Derek Crowther
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  5. Brian Fox
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  6. George R. Pettit
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  7. Peter L. Stern
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Additional information

B.F. and P.L.S. are supported by the Cancer Research Campaign

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Scheid, C., Prendiville, J., Jayson, G. et al. Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro. Cancer Immunol Immunother 39, 223–230 (1994). https://doi.org/10.1007/BF01525985

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  • DOI: https://doi.org/10.1007/BF01525985

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