An Immunotherapy Against Cancer Using Viral RNA

Ellen Lorraine Dore


In the human immune system, receptors and phosphokinase signaling cascades alert the body of the presence of a virus infection.  Recognized by cellular pattern-recognition receptors (PRR), viral RNA species trigger the activation of type I interferon (IFN-beta) and type III (IFN-lambda) innate immune pathways.  IFN induction ultimately leads to expression of antiviral genes that inhibit virus replication, and to adaptive cytotoxic T lymphocyte (CTL) responses that eliminate infected cells.  We hypothesize that an antiviral response triggered by viral RNA could directly activate an oncolytic pathway that kills tumor cells, or exposes tumor cells to antiviral CTL that are capable of targeting cells expressing tumor antigens on MHC I complexes on the cell surface.  Synthetic viral RNA (poly-I:C) was transfected into a panel of human lung and pancreatic tumor cell lines.  Transfected cells were assayed to determine interferon response by quantitative RT-PCR.  In human lung adenocarcinoma (A549) cells, poly I:C containing both low-molecular weight (LMW) and high-molecular weight (HMW) chains induced 1.6-4 fold expression of IFN-beta, IFN-lambdas (IL28 and IL29), and the antiviral gene MXA1, suggesting that this tumor cell type contains an intact PRR signaling pathway.  LMW poly-I:C induced 1-3 fold expression, while HMW poly-I:C showed 1.5-2.5 induction.  Assays to measure cell death and growth inhibition in A549, as well as IFN responses in other human lung (NCI-H23) and pancreatic (PaCa-2) tumor cells are ongoing.  By understanding IFN responses in human tumor cells, this project harnesses the antiviral capabilities of the immune system to develop new immunotherapies against cancer.


Cancer; Interferons; Oncolytic Virotherapy; Cancer Immunotherapy

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