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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.


Related in: MedlinePlus

Future prospective: mAbs (anticytotoxic T-lymphocyte-associated protein-4/anti-programmed death-1/anti-programmed death-ligand 1) against immune checkpoints encoded by the VV.Notes: mAbs engineered with the VV may enhance tumor cell death. After the replication of the virus in the cytosol, synthesis of mAbs would occur, followed by the inhibition of cytotoxic T-lymphocyte-associated protein 4, programmed death-1, and programmed death-ligand 1 may take place. It also causes inhibition of immune checkpoints that expressed by other uninfected cancer cells.Abbreviations: APCs, antigen-presenting cells; mAbs, monoclonal antibodies; VV, vaccinia virus.
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f5-ijn-11-4835: Future prospective: mAbs (anticytotoxic T-lymphocyte-associated protein-4/anti-programmed death-1/anti-programmed death-ligand 1) against immune checkpoints encoded by the VV.Notes: mAbs engineered with the VV may enhance tumor cell death. After the replication of the virus in the cytosol, synthesis of mAbs would occur, followed by the inhibition of cytotoxic T-lymphocyte-associated protein 4, programmed death-1, and programmed death-ligand 1 may take place. It also causes inhibition of immune checkpoints that expressed by other uninfected cancer cells.Abbreviations: APCs, antigen-presenting cells; mAbs, monoclonal antibodies; VV, vaccinia virus.

Mentions: Oncolytic virotherapy based on VV has proven its benefits in both clinical and preclinical studies. Because of the large size of the VV genome, genetic engineering (such as addition and deletion) is highly beneficial. Combination therapy with cell-cycle regulators, immune-checkpoint inhibitors, apoptosis inducers, and/or other molecules should be the focus of future research. Combinatorial treatment with monoclonal antibodies against immune checkpoint blockades has also been evaluated in recent clinical trials and has shown promising results. In addition, approaches with low toxicity and good efficacy must be taken into consideration. Although virologic and immunologic aspects of the mechanism of virotherapy have been well characterized, future studies should investigate the positive outcomes of oncolytic virotherapy using VV. At present, most of the preclinical studies are using xenograft models to investigate oncolytic effect of OVs; this approach should be replaced by immunocompetent animals, in order to take the immune system together to understand the actual coordinated efficacy OVs. This is very important for further translational research in oncolytic virotherapy as well as for the efficient combination therapy of OVs with immune checkpoint blockades (Figure 5). To elucidate immune interactions in cancer cells by OVs, more translational trials should be well designed and conducted. These approaches should also be considered in translational medicine, especially in future clinical trials.


Viruses as nanomedicine for cancer
Future prospective: mAbs (anticytotoxic T-lymphocyte-associated protein-4/anti-programmed death-1/anti-programmed death-ligand 1) against immune checkpoints encoded by the VV.Notes: mAbs engineered with the VV may enhance tumor cell death. After the replication of the virus in the cytosol, synthesis of mAbs would occur, followed by the inhibition of cytotoxic T-lymphocyte-associated protein 4, programmed death-1, and programmed death-ligand 1 may take place. It also causes inhibition of immune checkpoints that expressed by other uninfected cancer cells.Abbreviations: APCs, antigen-presenting cells; mAbs, monoclonal antibodies; VV, vaccinia virus.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-11-4835: Future prospective: mAbs (anticytotoxic T-lymphocyte-associated protein-4/anti-programmed death-1/anti-programmed death-ligand 1) against immune checkpoints encoded by the VV.Notes: mAbs engineered with the VV may enhance tumor cell death. After the replication of the virus in the cytosol, synthesis of mAbs would occur, followed by the inhibition of cytotoxic T-lymphocyte-associated protein 4, programmed death-1, and programmed death-ligand 1 may take place. It also causes inhibition of immune checkpoints that expressed by other uninfected cancer cells.Abbreviations: APCs, antigen-presenting cells; mAbs, monoclonal antibodies; VV, vaccinia virus.
Mentions: Oncolytic virotherapy based on VV has proven its benefits in both clinical and preclinical studies. Because of the large size of the VV genome, genetic engineering (such as addition and deletion) is highly beneficial. Combination therapy with cell-cycle regulators, immune-checkpoint inhibitors, apoptosis inducers, and/or other molecules should be the focus of future research. Combinatorial treatment with monoclonal antibodies against immune checkpoint blockades has also been evaluated in recent clinical trials and has shown promising results. In addition, approaches with low toxicity and good efficacy must be taken into consideration. Although virologic and immunologic aspects of the mechanism of virotherapy have been well characterized, future studies should investigate the positive outcomes of oncolytic virotherapy using VV. At present, most of the preclinical studies are using xenograft models to investigate oncolytic effect of OVs; this approach should be replaced by immunocompetent animals, in order to take the immune system together to understand the actual coordinated efficacy OVs. This is very important for further translational research in oncolytic virotherapy as well as for the efficient combination therapy of OVs with immune checkpoint blockades (Figure 5). To elucidate immune interactions in cancer cells by OVs, more translational trials should be well designed and conducted. These approaches should also be considered in translational medicine, especially in future clinical trials.

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