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

Navabi, H., Croston, D., Hobot, Jan, Clayton, Aled ORCID:, Zitvogel, L., Jasani, Bharat, Bailey-Wood, R., Wilson, Keith, Tabi, Zsuzsanna, Mason, Malcolm ORCID: and Adams, M. 2005. Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial. Blood Cells, Molecules, and Diseases 35 (2) , pp. 149-152. 10.1016/j.bcmd.2005.06.008

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Ovarian cancer; ascites-derived exosomes; clinical trial.
Publisher: Elsevier
ISSN: 1079-9796
Last Modified: 18 Mar 2023 02:08

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