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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

Important events in clinical trials of the vaccinia virus.Notes: This chronologic graph represents key achievements in oncolytic virotherapy. The first trial was started in 1964, and various subsequent trials are in different phases. Recently, the safety and efficacy of the vaccinia virus were proven by the results of Phases I and II clinical trials.
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f4-ijn-11-4835: Important events in clinical trials of the vaccinia virus.Notes: This chronologic graph represents key achievements in oncolytic virotherapy. The first trial was started in 1964, and various subsequent trials are in different phases. Recently, the safety and efficacy of the vaccinia virus were proven by the results of Phases I and II clinical trials.

Mentions: The oncolytic efficacy and safety of engineered VV strains were recently evaluated in patients with various types of cancers. Most of the clinical trials were completed at the Phase I level. JX-594, encoding GM-CSF with the disruption of vTK, caused significant regression of tumors in patients with various cancers. The main outcomes of these clinical trials are shown in Table 3.73,74 Other than that, the GL-ONC1 (GLV-1h68) from Benelux Corporation is currently studied in Phase I and Phase I/II clinical trials on human cancer patients GL-ONC.75 Important events in these clinical trials are summarized in Figure 4. In a Phase I clinical trial, an IT injection of JX-594 into the primary or metastatic liver tumors of 14 patients was well tolerated. The safety profile of JX-594 was evaluated in terms of viral replication, GM-CSF expression, and systemic dissemination. However, direct hyperbilirubinemia was observed as a dose-limiting toxicity.76 Another clinical trial was conducted in patients with advanced liver cancer to monitor the antivascular properties of JX-594. Interestingly, antihepatitis B virus (HBV) activity of JX-594 was observed in three patients with advanced refractory HBV-associated HCC. IT application of the virus (3×108 PFU) induced antivascular cytokines and targeted distant tumors in these patients. The suppression of HBV replication in the presence of JX-594 was first reported in this study. However, further studies are warranted because the results were shown in only three patients.77 The selective replication and infection of JX-594 in tumor tissues were confirmed in other clinical trials. IV infusion was shown to cause viral infection of metastatic tumors. These results were confirmed by pharmacokinetic and quantitative polymerase chain reaction analyses. The overall results revealed an antitumor effect of JX-594 in metastatic tumors in a dose-limiting manner.60


Viruses as nanomedicine for cancer
Important events in clinical trials of the vaccinia virus.Notes: This chronologic graph represents key achievements in oncolytic virotherapy. The first trial was started in 1964, and various subsequent trials are in different phases. Recently, the safety and efficacy of the vaccinia virus were proven by the results of Phases I and II clinical trials.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-11-4835: Important events in clinical trials of the vaccinia virus.Notes: This chronologic graph represents key achievements in oncolytic virotherapy. The first trial was started in 1964, and various subsequent trials are in different phases. Recently, the safety and efficacy of the vaccinia virus were proven by the results of Phases I and II clinical trials.
Mentions: The oncolytic efficacy and safety of engineered VV strains were recently evaluated in patients with various types of cancers. Most of the clinical trials were completed at the Phase I level. JX-594, encoding GM-CSF with the disruption of vTK, caused significant regression of tumors in patients with various cancers. The main outcomes of these clinical trials are shown in Table 3.73,74 Other than that, the GL-ONC1 (GLV-1h68) from Benelux Corporation is currently studied in Phase I and Phase I/II clinical trials on human cancer patients GL-ONC.75 Important events in these clinical trials are summarized in Figure 4. In a Phase I clinical trial, an IT injection of JX-594 into the primary or metastatic liver tumors of 14 patients was well tolerated. The safety profile of JX-594 was evaluated in terms of viral replication, GM-CSF expression, and systemic dissemination. However, direct hyperbilirubinemia was observed as a dose-limiting toxicity.76 Another clinical trial was conducted in patients with advanced liver cancer to monitor the antivascular properties of JX-594. Interestingly, antihepatitis B virus (HBV) activity of JX-594 was observed in three patients with advanced refractory HBV-associated HCC. IT application of the virus (3×108 PFU) induced antivascular cytokines and targeted distant tumors in these patients. The suppression of HBV replication in the presence of JX-594 was first reported in this study. However, further studies are warranted because the results were shown in only three patients.77 The selective replication and infection of JX-594 in tumor tissues were confirmed in other clinical trials. IV infusion was shown to cause viral infection of metastatic tumors. These results were confirmed by pharmacokinetic and quantitative polymerase chain reaction analyses. The overall results revealed an antitumor effect of JX-594 in metastatic tumors in a dose-limiting manner.60

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