Bispecific antibody CD73xEpCAM selectively inhibits the adenosine-mediated immunosuppressive activity of carcinoma-derived extracellular vesicles

Ploeg, Emily M.; Ke, Xiurong; Britsch, Isabel; Hendriks, Mark A J M; Zant, Femke A van der; Kruijff, Schelto; Samplonius, Douwe F.; Zhang, Hao; Helfrich, Wijnand

doi:10.1016/j.canlet.2021.08.037

Cited by 14 publications

(15 citation statements)

References 29 publications

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“…Similarly, another e6 S.İ. Göktuna study put forwards that CRC-derived extracellular vesicles may drive the immunosuppressive activity of CD73 expressed in cancer cells which may be targeted via a bispecific antibody (CD73×EpCAM) (Ploeg et al 2021).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Differential Expression Patterns of the Extracellular Purinergic Enzymes in Colorectal Cancer

Göktuna

2022

Trakya University Journal of Natural Sciences

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Objective: The aim of this study is to characterize tumor cell specific expression of purinergic ecto-enzymes CD39 and CD73 and to associate prognostic significance of these expression patterns in colorectal cancer (CRC) patients. Methods: Gene expression of the target genes in various CRC cell lines were assessed via WB and RT-PCR. Additionally, tumor vs stromal cell expression of the target genes was analyzed from publicly available patient expression datasets. Finally, the correlation between CD39 and CD73 expression with patient prognosis was analyzed via TCGA datasets. Results: In CRC cell lines CD39 found to be not expressed at all while CD73 was expressed extensively in most cell lines via WB and RT-CR analyses. Patient microarray expression data confirmed the results from CRC cells lines that CD39 expression was very low in epithelial/tumor cells relative to other stromal cell types yet CD73 was expressed abundantly in every cell type within patient tumor samples. Interestingly, CD39 expression in patient tumors was correlated with favorable prognosis while CD73 expression was associated with worse prognosis. Conclusion: Although CD39 and CD73 are related enzymes involved in extracellular purinergic signaling, their expression patterns in tumor cells and prognostic effects in patients show opposing outcomes. Therefore, better insights in understanding the functional involvement of purinergic ecto-enzymes in colorectal tumor development is needed via further mechanistical studies.

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Section: Discussionmentioning

confidence: 99%

Characterization of Differential Expression Patterns of the Extracellular Purinergic Enzymes in Colorectal Cancer

Göktuna

2022

Trakya University Journal of Natural Sciences

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“…Both ATP and adenosine have been found in tumor cell-derived EVs ( 23 ), and perforin secreted by activated cytotoxic T cells can disrupt the EV membrane and lead to adenosine release that will in turn inhibit cytotoxic responses ( 21 ). Antibody-mediated blockade of CD73 enzymatic activity revokes immune suppression by tumor-derived EVs in vitro , highlighting the importance of the purinergic pathway in immune suppression in the context of tumors ( 29 ). EVs with purinergic enzyme activity travel far beyond the tumor and are detected in peripheral blood, where their presence correlates with cancer progression ( 30 , 45 , 49 ).…”

Section: Control Of the Immune Response By Extracellular Vesicles Wit...mentioning

confidence: 99%

Purinergic enzymes on extracellular vesicles: immune modulation on the go

Winzer,

Nguyen,

Schoppmeier

et al. 2024

Front. Immunol.

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An increase in the extracellular concentration of ATP as a consequence of cellular stress or cell death results in the activation of immune cells. To prevent inflammation, extracellular ATP is rapidly metabolized to adenosine, which deploys an anti-inflammatory signaling cascade upon binding to P1 receptors on immune cells. The ectonucleotidases necessary for the degradation of ATP and generation of adenosine are present on the cell membrane of many immune cells, and their expression is tightly regulated under conditions of inflammation. The discovery that extracellular vesicles (EVs) carry purinergic enzyme activity has brought forward the concept of EVs as a new player in immune regulation. Adenosine-generating EVs derived from cancer cells suppress the anti-tumor response, while EVs derived from immune or mesenchymal stem cells contribute to the restoration of homeostasis after infection. Here we will review the existing knowledge on EVs containing purinergic enzymes and molecules, and discuss the relevance of these EVs in immune modulation and their potential for therapy.

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“…Ploeg and his team attempted to bypass this EVs-mediated immune resistance to CRC. They developed a novel bispecific antibody CD73xEpCAM, which could bind to the surface marker EpCAM of EVs and inhibit CD73 (GPI-anchored ecto 5'-nucleotidase), thereby effectively enhancing the immune activity [ 45 ].…”

Section: Extracellular Vesicles Regulate Drug Resistance In Colorecta...mentioning

confidence: 99%

The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends

et al. 2023

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Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed. Graphical Abstract

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Bispecific antibody CD73xEpCAM selectively inhibits the adenosine-mediated immunosuppressive activity of carcinoma-derived extracellular vesicles

Cited by 14 publications

References 29 publications

Characterization of Differential Expression Patterns of the Extracellular Purinergic Enzymes in Colorectal Cancer

Characterization of Differential Expression Patterns of the Extracellular Purinergic Enzymes in Colorectal Cancer

Purinergic enzymes on extracellular vesicles: immune modulation on the go

The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends

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