Exosome-based liquid biopsies in cancer: opportunities and challenges

Wang, Yu; Hurley, James; Roberts, D.H.; Chakrabortty, Sudipto K.; Enderle, Daniel; Noerholm, Mikkel; Breakefield, Xandra O.; Skog, Johan

doi:10.1016/j.annonc.2021.01.074

Cited by 554 publications

(421 citation statements)

References 130 publications

(163 reference statements)

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“…blood, lymph, cerebrospinal fluid, vitreous, interstitial fluids, etc.) 49, 58 . Furthermore, there is no evidence of adverse effects of allogeneic exosome transfer, whether of purified exosomes (from amniotic fluid, blood, etc.)…”

Section: Discussionmentioning

confidence: 99%

Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination

Tsai

Guo

Sedgwick

et al. 2020

Preprint

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Background: In less than a year from its zoonotic entry into the human population, SARS-CoV-2 has infected more than 45 million people, caused 1.2 million deaths, and induced widespread societal disruption. Leading SARS-CoV-2 vaccine candidates immunize with the viral spike protein delivered on viral vectors, encoded by injected mRNAs, or as purified protein. Here we describe a different approach to SARS-CoV-2 vaccine development that uses exosomes to deliver mRNAs that encode antigens from multiple SARS-CoV-2 structural proteins. Approach: Exosomes were purified and loaded with mRNAs designed to express (i) an artificial fusion protein, LSNME, that contains portions of the viral spike, nucleocapsid, membrane, and envelope proteins, and (ii) a functional form of spike. The resulting combinatorial vaccine, LSNME/SW1, was injected into thirteen weeks-old, male C57BL/6J mice, followed by interrogation of humoral and cellular immune responses to the SARS-CoV-2 nucleocapsid and spike proteins, as well as hematological and histological analysis to interrogate animals for possible adverse effects. Results: Immunized mice developed CD4+, and CD8+ T-cell reactivities that respond to both the SARS-CoV-2 nucelocapsid protein and the SARS-CoV-2 spike protein. These responses were apparent nearly two months after the conclusion of vaccination, as expected for a durable response to vaccination. In addition, the spike-reactive CD4+ T-cells response was associated with elevated expression of interferon gamma, indicative of a Th1 response, and a lesser induction of interleukin 4, a Th2-associated cytokine. Vaccinated mice showed no sign of altered growth, injection-site hypersensitivity, change in white blood cell profiles, or alterations in organ morphology. Consistent with these results, we also detected moderate but sustained anti-nucleocapsid and anti-spike antibodies in the plasma of vaccinated animals. Conclusion: Taken together, these results validate the use of exosomes for delivering functional mRNAs into target cells in vitro and in vivo, and more specifically, establish that the LSNME/SW1 vaccine induced broad immunity to multiple SARS-CoV-2 proteins.

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Section: Discussionmentioning

confidence: 99%

Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination

Tsai

Guo

Sedgwick

et al. 2020

Preprint

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“…It 2as recently suggested that exosomes have several advantages over other biological components in liquid biopsies [44,45]. Indeed, among different moieties present in liquid biopsies, EV are stable in circulation and protect their cargos from degradation.…”

Section: Liquid Biopsiesmentioning

confidence: 99%

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

Marimpietri

Airoldi

Faini

et al. 2021

IJMS

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The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.

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“…The DNA that is searched in this blood-based test is called circulating tumor DNA (ctDNA), because, as the name suggests, cancer cells release it into the peripheral blood from necrotic and apoptotic processes during carcinogenesis [11]. Moreover, it is also actively released from exosomes [12].…”

Section: Ctdna Methylation-sept9 Methylation Assaysmentioning

confidence: 99%

Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

Ferrari¹,

Neefs²,

Hoeck³

et al. 2021

Preprint

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Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

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Exosome-based liquid biopsies in cancer: opportunities and challenges

Cited by 554 publications

References 130 publications

Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination

Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

Towards Novel Non-Invasive Colorectal Cancer Screening Methods: A Comprehensive Review

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