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

Navabi, H.; Croston, D.; Hobot, Jan A.; Clayton, Aled; Zitvogel, Laurence; Jasani, Bharat; Bailey‐Wood, R.; Wilson, Keith; Tabi, Zsuzsanna; Mason, Malcolm David; Adams, Malcolm

doi:10.1016/j.bcmd.2005.06.008

Cited by 95 publications

(75 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the group 2, every 3 PBMCs were co-cultured with DC -for 7 days in the same conditions as group 1. In the group 3, every 3x10 4 PBMCs were cultured with exosomes derived from 10 ml ascites for 7 days in the same conditions as group 1. In the group 4, PBMCs cultured without DCs or exosomes for 7 days in the same conditions as group 1.…”

Section: The In Vitro Anti-ovarian Cancer Effect Of the Pbmcs Stimulamentioning

confidence: 99%

“…Precursor cells (3x10 4 ) were cultured with exosomes derived from 10 ml ascites, and the same number of precursor cells without exosomes were the control group. All these cells were cultured in RPMI-1640 containing 100 g/ml GM-CSF, 50 ng/ml IL-4 and 10% human AB serum.…”

Section: Effect Of Exosomes On Anti-tumor Immunologic Function Of Dcsmentioning

confidence: 99%

“…But our study was different from that of Andre et al (9) in some aspects. In their study, 3x10 4 DCs were cultured with exosomes equivalent to 10 ml malignant effusion or culture supernatant for 2 h. Peripheral blood lymphocytes were then added at a ratio of three lymphocytes to one DC. They stimulated the peripheral blood lymphocytes in vitro once a week for a total of two or three stimulations.…”

Section: The In Vitro Anti-ovarian Cancer Cytotoxic Activity Of the Pmentioning

confidence: 99%

“…There are still many puzzles of ovarian cancer, including the relationship between the tumor and the host immune system, and the mechanisms of the development, invasion and metastasis of the tumor. Exosomes are a kind of microvesicles released by many types of cells such as tumor cell (1)(2)(3)(4), antigen presenting cells (APC) (5,6) and epithelial cells (7,8). Recent research revealed that exosomes purified from the ascites of patient with ovarian cancer contain some immunological-effect molecules (9).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

2011

View full text Add to dashboard Cite

Abstract. This study was performed to identify the origin of the ascites-derived exosomes from patients with ovarian cancer and to observe the effect of exosomes on anti-tumor immunity. Exosomes were isolated from the ascites of patients with ovarian epithelial cancer by ultracentrifugation plus density gradient centrifugation. The origin of exosomes was identified by immunoelectronmicroscopy (IEM). The growth curve of the tumor cell line SKOV3 cultured with or without exosomes was analyzed. The apoptosis of autogeneic tumor cells (ATCs) and SKOV3 cells affected by exosomes was measured by flow cytometry (FCM) and light phase contrast microscopy. The cytotoxic effect of the peripheral blood mononuclear cells (PBMCs) stimulated by exosomes and/or dendritic cells (DCs) on ovarian cancer cells was measured using a CCK-8 assay. The levels of IFN-Á released by PBMCs stimulated by exosomes and/or DCs were measured by ELISA. The apoptosis of PBMCs and DCs affected by exosomes was measured by FCM and light microscopy. Whether the mature process of DCs was affected by exosomes was studied by FCM. The ratio of CD4 + T cell and CD8 + T cell were measured by FCM. FasL and TRAIL molecules on exosomes were detected by Western blot analysis. The human FasL antagonistic antibody was used to block the apoptosis of DCs and PBMCs induced by exosomes. The receptors of TRAIL DR4 and DR5 on PBMCs and DCs were detected by FCM. In 41 patients examined, we isolated exosomes from the ascites of 35 patients. We detected TCR, CD20, HLA-DR, B7-2, HER2/neu, CA125 and Histone H 2 A on exosomes. We found that exosomes might impair the cytotoxic activity of PBMCs when DCs are present. We found that exosomes had no effect on the growth and apoptosis of SKOV3 cells. However, exosomes may induce apoptosis of precursors, mature DCs and PBMCs. We found that FasL and TRAIL were present in the exosome suspension and addition of an anti-FasL antibody may decrease the percentage of apoptosis of DCs and PBMCs. We conclude that exosomes exist in ascites of 85.4% of patients with ovarian cancer. Moreover, these exosomes may be of multi-origin. Exosomes had no effect on the growth and apoptosis of tumor cells but impaired the cytotoxic activity of PBMCs in the presence of DCs. Exosomes also may induce apoptosis of the precursors of DCs, DCs and PBMCs. FasL and TRAIL on exosomes may partly account for the apoptosis of cells of the immune system.

show abstract

Section: The In Vitro Anti-ovarian Cancer Effect Of the Pbmcs Stimulamentioning

confidence: 99%

Section: Effect Of Exosomes On Anti-tumor Immunologic Function Of Dcsmentioning

confidence: 99%

Section: The In Vitro Anti-ovarian Cancer Cytotoxic Activity Of the Pmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

2011

View full text Add to dashboard Cite

show abstract

“…Their physiological functions are diverse, generally related to the functions of the parent cell (28). Exosomes are produced by tumors in vivo and they are often abundant in malignant effusions for example in advanced ovarian carcinoma (29) and pleural malignant mesothelioma (30). Exosomes released from malignified epithelial cells that no longer respect their basal membranes but grow invasively may be useful biomarkers in blood plasma (31)(32)(33)(34) and urine (35) in some cancer types.…”

mentioning

confidence: 99%

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

Tavoosidana

Ronquist

Darmanis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

199

173

View full text Add to dashboard Cite

Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.

show abstract

Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunotherapy

et al. 2019

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are secreted by almost all cells. They contain proteins, lipids, and nucleic acids which are delivered from the parent cells to the recipient cells. Thereby, they function as mediators of intercellular communication and molecular transfer. Recent evidences suggest that exosomes, a small subset of EVs, are involved in numerous physiological and pathological processes and play essential roles in remodeling the tumor immune microenvironment even before the occurrence and metastasis of cancer. Exosomes derived from tumor cells and host cells mediate their mutual regulation locally or remotely, thereby determining the responsiveness of cancer therapies. As such, tumor‐derived circulating exosomes are considered as noninvasive biomarkers for early detection and diagnosis of tumor. Exosome‐based therapies are also emerging as cutting‐edge and promising strategies that could be applied to suppress tumor progression or enhance anti‐tumor immunity. Herein, the current understanding of exosomes and their key roles in modulating immune responses, as well as their potential therapeutic applications are outlined. The limitations of current studies are also presented and directions for future research are described.

show abstract

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

Cited by 95 publications

References 17 publications

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer

Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunotherapy

Contact Info

Product

Resources

About