Background While chemo- and radio-therapies were considered the first-line treatment for most cancers, their serious side effects have led to continuous innovation and discovery of new cancer therapies. Oncolytic viruses (OVs), either naturally occurred or genetically engineered to selectively target and lyse cancer cells without harming normal tissues, have emerged as the next remarkable wave in cancer immunotherapy. OVs possess a magnitude of mechanisms to elicit anti-tumor immune response, including the infection in cancer cells causing the viral replication and cell lysis. In addition to OVs innate cytotoxicity, further anti-tumor enhancement can be achieved via inserting tumor-associated antigen (TAA)/immunomodulatory genes by genetic engineering technology, leading to the release of inflammatory and immunoregulatory cytokines. This in effect, causes the tumor to become “hot” and detectable by other immune cells, which are subsequently stimulated to eradicate tumor. Our recent study assessed the effect of modified OVs (mOVs) engineered with immunomodulatory genes in the in vitro assays with various immune cells including T, natural killer (NK) and monocyte-derived dendritic cells (moDC).
The expression of exogenous immunomodulatory genes, in different tumor cells infected with mock or mOV, was detected by flow-cytometry and ELISA.
Cytotoxicity of mOV on different tumor cell lines were evaluated by CCK-8 and plaque assays.
The apoptosis induced by mOV in different tumor cells was analyzed by flow-cytometry.
The activation of T cells in co-culture with mOV-infected tumor cells was evaluated by the ELISA detection of IFN-γ.
T or NK cells were treated with supernatants from the culture of mOV-infected tumor cells. Released IFN-γ was detected by ELISA.
CD8+ T cells were co-cultured with mOV-treated moDC cells, and the T cell activation was evaluated by flow-cytometry and ELISA.
Results A susceptible cell line was identified for mOV infection, which had high expression efficiency of exogenous immunomodulatory genes.
mOV induced a cytotoxicity on the susceptible cells through apoptosis effect.
mOV-infected tumor cells and the harvested surpernatants significantly promoted the activation of T or NK cells.
mOV treatment promoted the maturation of moDCs and the secretion of IFN-γ by CD8+ T cells.
Conclusions Modified OV significantly induced cytotoxicity on the susceptible tumor cells, and promoted the activation of T, NK and moDC immune cells with increased inflammatory cytokine secretion. Our study suggested an effective approach for the development and validtion of the next generation of oncolytic viruses being more potent in both the direct tumor killing and immune activation.
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