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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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Infection with OVs enhances immune activation against cancer cells.Notes: Infection with OVs induces genotoxicity and ER stress in cancer cells. IFN-1 released from cancer cells activates NK cells and CD8+ T-cells. This event induces cytotoxicity and cell death in surrounding uninfected cancer cells. Conversely, oncolysis induces the production of neoantigens by cancer cells, which are presented by APCs to CD4+ and CD8+ T-cells for activation. Activated CD4+ T-cells secrete IL-2 and enhance the cytotoxicity of CD8+ T-cells. These mechanisms enhance immune activation against cancer cells. Data from Kaufman et al.8Abbreviations: APC, antigen-presenting cell; CD, cluster of differentiation; ER, endoplasmic reticulum; IFNs, interferons; IL, interleukin; NK, natural killer; OVs, oncolytic viruses; ROS, reactive oxygen species.
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f1-ijn-11-4835: Infection with OVs enhances immune activation against cancer cells.Notes: Infection with OVs induces genotoxicity and ER stress in cancer cells. IFN-1 released from cancer cells activates NK cells and CD8+ T-cells. This event induces cytotoxicity and cell death in surrounding uninfected cancer cells. Conversely, oncolysis induces the production of neoantigens by cancer cells, which are presented by APCs to CD4+ and CD8+ T-cells for activation. Activated CD4+ T-cells secrete IL-2 and enhance the cytotoxicity of CD8+ T-cells. These mechanisms enhance immune activation against cancer cells. Data from Kaufman et al.8Abbreviations: APC, antigen-presenting cell; CD, cluster of differentiation; ER, endoplasmic reticulum; IFNs, interferons; IL, interleukin; NK, natural killer; OVs, oncolytic viruses; ROS, reactive oxygen species.

Mentions: As stated in the “Cancer cell lysis by OVs” section, the therapeutic efficacy of OVs depends on the combined effect of direct cancer cell lysis and indirect activation of antitumor immune responses. The immune responses induced by OVs have a range of effects. The antiviral immune response is activated upon OV infection. Genotoxicity and endoplasmic reticulum stress lead to the upregulation of reactive oxygen species generation and the initiation of antiviral cytokine production.31 Consequently, infected cancer cells produce reactive oxygen species, antiviral cytokines, and Type I IFNs, thereby stimulating antigen-presenting cells, CD8+ T-cells, and NK cells (Figure 1). However, viral progeny, PAMPs, danger-associated molecular patterns (DAMPs), and tumor-associated antigens (TAAs) including neoantigens are released after oncolysis. The released viral progeny propagates the infection. The PAMPs, consisting of viral particles and DAMPs, induce host cell proteins, trigger the activation of TLRs, and stimulate the immune system. As a result of these immune-stimulatory occurrences, antigen-presenting cells capture the released TAAs and neoantigens. Together, these events instigate immune responses toward both virally infected and uninfected cancer cells through de novo immune responses.32


Viruses as nanomedicine for cancer
Infection with OVs enhances immune activation against cancer cells.Notes: Infection with OVs induces genotoxicity and ER stress in cancer cells. IFN-1 released from cancer cells activates NK cells and CD8+ T-cells. This event induces cytotoxicity and cell death in surrounding uninfected cancer cells. Conversely, oncolysis induces the production of neoantigens by cancer cells, which are presented by APCs to CD4+ and CD8+ T-cells for activation. Activated CD4+ T-cells secrete IL-2 and enhance the cytotoxicity of CD8+ T-cells. These mechanisms enhance immune activation against cancer cells. Data from Kaufman et al.8Abbreviations: APC, antigen-presenting cell; CD, cluster of differentiation; ER, endoplasmic reticulum; IFNs, interferons; IL, interleukin; NK, natural killer; OVs, oncolytic viruses; ROS, reactive oxygen species.
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Related In: Results  -  Collection

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

f1-ijn-11-4835: Infection with OVs enhances immune activation against cancer cells.Notes: Infection with OVs induces genotoxicity and ER stress in cancer cells. IFN-1 released from cancer cells activates NK cells and CD8+ T-cells. This event induces cytotoxicity and cell death in surrounding uninfected cancer cells. Conversely, oncolysis induces the production of neoantigens by cancer cells, which are presented by APCs to CD4+ and CD8+ T-cells for activation. Activated CD4+ T-cells secrete IL-2 and enhance the cytotoxicity of CD8+ T-cells. These mechanisms enhance immune activation against cancer cells. Data from Kaufman et al.8Abbreviations: APC, antigen-presenting cell; CD, cluster of differentiation; ER, endoplasmic reticulum; IFNs, interferons; IL, interleukin; NK, natural killer; OVs, oncolytic viruses; ROS, reactive oxygen species.
Mentions: As stated in the “Cancer cell lysis by OVs” section, the therapeutic efficacy of OVs depends on the combined effect of direct cancer cell lysis and indirect activation of antitumor immune responses. The immune responses induced by OVs have a range of effects. The antiviral immune response is activated upon OV infection. Genotoxicity and endoplasmic reticulum stress lead to the upregulation of reactive oxygen species generation and the initiation of antiviral cytokine production.31 Consequently, infected cancer cells produce reactive oxygen species, antiviral cytokines, and Type I IFNs, thereby stimulating antigen-presenting cells, CD8+ T-cells, and NK cells (Figure 1). However, viral progeny, PAMPs, danger-associated molecular patterns (DAMPs), and tumor-associated antigens (TAAs) including neoantigens are released after oncolysis. The released viral progeny propagates the infection. The PAMPs, consisting of viral particles and DAMPs, induce host cell proteins, trigger the activation of TLRs, and stimulate the immune system. As a result of these immune-stimulatory occurrences, antigen-presenting cells capture the released TAAs and neoantigens. Together, these events instigate immune responses toward both virally infected and uninfected cancer cells through de novo immune responses.32

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