Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial

H. Navabi, D. Croston, J. Hobot, A. Clayton, L. Zitvogel, B. Jasani, R. Bailey-Wood, K. Wilson, Z. Tabi, M. D. Mason, M. Adams

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

Despite initial response to chemotherapy, at least 50% of ovarian cancer patients will relapse within 18 months. Progression-free survival is related to tumour infiltration with cytotoxic T lymphocytes (CTL). We recently demonstrated that CD8+ T cell responses to recall antigens improve following tumour response to chemotherapy. Vaccination designed to expand CTL, specific for tumour-associated antigens, may be a means of improving outcome. We are planning a clinical trial in advanced ovarian cancer patients undergoing chemotherapy using a combination of a Toll-like receptor 3 (TLR3) agonist and tumour-associated ascites-derived exosomes. Tumour-derived exosomes are a potential source of tumour antigens able to induce CD8+ T cell responses when loaded on mature dendritic cells (DC). DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen®) which is a TLR-3 agonist. Here, we describe the development of a method suitable for the preparation of GMP-grade exosomes from the ascites fluid of ovarian cancer patients, and the methods used for the molecular and immunological characterisation of these exosomes preceding their use in a clinical trial.

Original languageEnglish
Pages (from-to)149-152
Number of pages4
JournalBlood Cells, Molecules, and Diseases
Volume35
Issue number2
DOIs
Publication statusPublished - 2005

Keywords

  • Ascites-derived exosomes
  • Clinical trial
  • Ovarian cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

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