Phase I Clinical Trial of Autologous Ascites-derived Exosomes Combined With GM-CSF for Colorectal Cancer

By Shengming Dai, D. Wei, Zhen Wu, Xiangyang Zhou, Xiaomou Wei, Haixin Huang, Gui-sheng Li. Molecular Therapy, 2008

772 citations recorded by the source corpus.

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/D2O 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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4ed45c142023f4ac0202e7d76851668db8fd0f1d

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Citations in the corpus

Classification, Functions, and Clinical Relevance of Extracellular Vesicles (2012, background): “Patients treated with the combination therapy showed beneficial tumor-specific antitumor cytotoxic T lymphocyte response (Dai et al., 2008).”
Exosome-Based Cell-Cell Communication in the Tumor Microenvironment (2018, background): “Common strategies involve genetic modification of exosomes-producing cells in order to modify exosomes content, including IL2 (Yang et al., 2007) and IL18 (Dai et al., 2008) and improve exosome-driven immunogenicity.”
Standardization of sample collection, isolation and analysis methods in extracellular vesicle research (2013, neutral): “…been isolated from biofluids including pleural effusions (33), plasma (34,35), ocular effluent and aqueous humor (36), breast milk (35,37), ascites (38,39), amniotic fluid (40,41), semen (‘‘prostasomes’’ and ‘‘epididymosomes’’) (42 (cid:2) 50), saliva (35,41,51,52), nasal secretions (53),…”
Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression (2018, background): “These findings have led to investigating the use of cancer-derived EVs as antitumoral vaccines (143, 144).”
Advances in therapeutic applications of extracellular vesicles (2019, methodology): “Colon cancer (105) Phase 1, n = 40 Ascites, autologous ± GM-CSF–induced CEA Safe, well tolerated; 1 stable disease, 1 minor response (both in CEA group).”
Innovative approaches for cancer treatment: current perspectives and new challenges (2019, methodology): “In a phase I trial, ascites-derived exosomes supplemented with granulocyte-macrophage colony stimulating factor (GM-CSF) have been administered to colorectal cancer patients, soliciting a tumour-specific immune response [93].”
Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, neutral): “EVs for anti-tumour immunotherapy (30) (Table I).”
EVpedia: a community web portal for extracellular vesicles research (2015, background): “…biological fluids, such as amniotic fluid, ascites, breast milk, plasma, saliva, semen, serum and urine (Asea et al., 2008; Caby et al., 2005; Cheng et al., 2014a, b; Dai et al., 2008; George et al., 1982; Lässer et al., 2011; Poliakov et al., 2009; Raj et al., 2012; Witwer et al., 2013).”