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Mol Ther. 2008 Apr;16(4):782-90. doi: 10.1038/mt.2008.1. Epub 2008 Feb 5.

Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer.

Author information

1
Department of Oncology, Institute of Clinical Medicine, The Fourth Hospital Affiliated to Guangxi Medical University, Liuzhou, People's Republic of China. shengming_dai@yahoo.com

Abstract

Exosomes are small membrane vesicles that are secreted by a multitude of cell types. The exosomes derived from dendritic cells (Dex), tumor cells (Tex), and malignant effusions demonstrate immunomodulatory functions, and are even under clinical trial for cancer treatments. In this study we report the phase I clinical trial of the ascites-derived exosomes (Aex) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) in the immunotherapy of colorectal cancer (CRC). The Aex isolated by sucrose/D(2)O density gradient ultracentrifugation are 60-90-nm vesicles that contain the diverse immunomodulatory markers of exosomes and tumor-associated carcinoembryonic antigen (CEA). Totally 40 patients (HLA-A0201(+)CEA(+)) with advanced CRC were enrolled in the study, and randomly assigned to treatments with Aex alone or Aex plus GM-CSF. Patients in both groups received a total of four subcutaneous immunizations at weekly intervals. We found that both therapies were safe and well tolerated, and that Aex plus GM-CSF but not Aex alone can induce beneficial tumor-specific antitumor cytotoxic T lymphocyte (CTL) response. Therefore, our study suggests that the immunotherapy of CRC with Aex in combination with GM-CSF is feasible and safe, and thus can serve as an alternative choice in the immunotherapy of advanced CRC.

PMID:
18362931
DOI:
10.1038/mt.2008.1
[Indexed for MEDLINE]
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