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Viruses as nanomedicine for cancer

View Article: PubMed Central - PubMed

ABSTRACT

Oncolytic virotherapy, a type of nanomedicine in which oncolytic viruses (OVs) are used to selectively infect and lyse cancer cells, is an emerging field in cancer therapy. Some OVs exhibit a specific tropism for cancer cells, whereas others require genetic modification to enhance their binding with and entry into cancer cells. OVs both kill tumor cells and induce the host’s immune response against tumor cells. Armed with antitumor cellular molecules, antibodies, and/or in combination with anticancer drugs, OVs can accelerate the lysis of cancer cells. Among the OVs, vaccinia virus has been the focus of preclinical and clinical research because of its many favorable properties. In this review, the basic mechanisms of action of OVs are presented, including their entry, survival, tumor lysis, and immune activation, and the latest research in vaccinia virus-based virotherapy and its status as an anticancer nanomedicine in prospective clinical trials are discussed.

No MeSH data available.


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Vaccinia virus entry mechanism.Notes: The vaccinia virus enters through endocytosis via two different mechanisms: A, lysosome-mediated entry; B, direct replication in the cytosol. ER acts as a factory for virus replication. Data from Tolonen et al.46Abbreviation: ER, endoplasmic reticulum.
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f2-ijn-11-4835: Vaccinia virus entry mechanism.Notes: The vaccinia virus enters through endocytosis via two different mechanisms: A, lysosome-mediated entry; B, direct replication in the cytosol. ER acts as a factory for virus replication. Data from Tolonen et al.46Abbreviation: ER, endoplasmic reticulum.

Mentions: Four forms of the virus exist during the life cycle of VV: intracellular mature virion (IMV), cell-associated enveloped virion (CEV), and extracellular enveloped virion (EEV). Among them, IMV and EEV are seen most often during assembly, often during assembly.42 VV enters tumor cells by endocytosis, during which direct fusion of the virus to the plasma membrane leads to it being engulfed. Glycosaminoglycan, such as heparan sulfate that is located on the cell surface, mediates VV and host cell interaction in which VV A27L protein plays a role in binding with heparin sulfate. Heparan sulfate–virus interaction might induce conformation rearrangements that may enhance the subsequent fusion events.43 For the direct fusion of the mature virions released from infected cells, four proteins (including H3, A26, A27, and D8) are necessary. These proteins form a complex with laminin, integrin, and CD98. A cytoplasmic adapter protein, TRAF2, facilitates VV entry through direct fusion at the plasma membrane. Enclosure within endocytic vesicles protects the virus from circulating antibodies.44 The low pH of the TME facilitates endosomal-mediated entry of the virus into cancer cells. Endoplasmic reticulum acts as a factory for viral replication in the cytosol (Figure 2).45,46 Upon virus infection, the mitogen-activated protein kinase- and cAMP-dependent protein kinase-mediated cell-signaling pathways are induced to achieve viral multiplication inside the cells. In general, the coordination of viral proteins and host cell factors facilitates the endocytosis of VV.47


Viruses as nanomedicine for cancer
Vaccinia virus entry mechanism.Notes: The vaccinia virus enters through endocytosis via two different mechanisms: A, lysosome-mediated entry; B, direct replication in the cytosol. ER acts as a factory for virus replication. Data from Tolonen et al.46Abbreviation: ER, endoplasmic reticulum.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036661&req=5

f2-ijn-11-4835: Vaccinia virus entry mechanism.Notes: The vaccinia virus enters through endocytosis via two different mechanisms: A, lysosome-mediated entry; B, direct replication in the cytosol. ER acts as a factory for virus replication. Data from Tolonen et al.46Abbreviation: ER, endoplasmic reticulum.
Mentions: Four forms of the virus exist during the life cycle of VV: intracellular mature virion (IMV), cell-associated enveloped virion (CEV), and extracellular enveloped virion (EEV). Among them, IMV and EEV are seen most often during assembly, often during assembly.42 VV enters tumor cells by endocytosis, during which direct fusion of the virus to the plasma membrane leads to it being engulfed. Glycosaminoglycan, such as heparan sulfate that is located on the cell surface, mediates VV and host cell interaction in which VV A27L protein plays a role in binding with heparin sulfate. Heparan sulfate–virus interaction might induce conformation rearrangements that may enhance the subsequent fusion events.43 For the direct fusion of the mature virions released from infected cells, four proteins (including H3, A26, A27, and D8) are necessary. These proteins form a complex with laminin, integrin, and CD98. A cytoplasmic adapter protein, TRAF2, facilitates VV entry through direct fusion at the plasma membrane. Enclosure within endocytic vesicles protects the virus from circulating antibodies.44 The low pH of the TME facilitates endosomal-mediated entry of the virus into cancer cells. Endoplasmic reticulum acts as a factory for viral replication in the cytosol (Figure 2).45,46 Upon virus infection, the mitogen-activated protein kinase- and cAMP-dependent protein kinase-mediated cell-signaling pathways are induced to achieve viral multiplication inside the cells. In general, the coordination of viral proteins and host cell factors facilitates the endocytosis of VV.47

View Article: PubMed Central - PubMed

ABSTRACT

Oncolytic virotherapy, a type of nanomedicine in which oncolytic viruses (OVs) are used to selectively infect and lyse cancer cells, is an emerging field in cancer therapy. Some OVs exhibit a specific tropism for cancer cells, whereas others require genetic modification to enhance their binding with and entry into cancer cells. OVs both kill tumor cells and induce the host’s immune response against tumor cells. Armed with antitumor cellular molecules, antibodies, and/or in combination with anticancer drugs, OVs can accelerate the lysis of cancer cells. Among the OVs, vaccinia virus has been the focus of preclinical and clinical research because of its many favorable properties. In this review, the basic mechanisms of action of OVs are presented, including their entry, survival, tumor lysis, and immune activation, and the latest research in vaccinia virus-based virotherapy and its status as an anticancer nanomedicine in prospective clinical trials are discussed.

No MeSH data available.


Related in: MedlinePlus