Abstract
With the progress of immunotherapy in cancer, oncolytic viruses (OVs) have attracted more and more attention during the past decade. Due to their cancer-selective and immunogenic properties, OVs are considered ideal candidates to be combined with immunotherapy to increase both specificity and efficacy in cancer treatment. OVs preferentially replicate in and lyse cancer cells, resulting in in situ autovaccination leading to adaptive anti-virus and anti-tumor immunity. The main challenge in OV approaches is how to redirect the host immunity from anti-virus to anti-tumor and optimize the clinical outcome of cancer patients. Here, we summarize the conceptual updates on oncolytic virotherapy and immunotherapy in cancer, and the development of strategies to enhance the virus-mediated anti-tumor immune response, including: (1) arm OVs with cytokines to modulate innate and adaptive immunity; (2) combining OVs with immune checkpoint inhibitors to release T cell inhibition; (3) combining OVs with immune co-stimulators to enhance T cell activation. Future studies need to be enforced on developing strategies to augment the systemic effect on metastasized tumors.
Highlights
The history of cancer therapy is a witness of toxicity and failure of efficacy despite numerous efforts to identify druggable cancer targets for personalized and targeted treatments.Emerging evidence indicates that the main challenges in developing efficacious and safe cancer therapeutics are heterogeneity, even within a single cancer, and the evolution of cancer cells during therapy [1,2]
Combination of oncolytic viruses (OVs) with immune checkpoint blockade (ICR), or with agonist antibody or expression of the co-stimulatory ligand (CSL) to bind with the cothrough antibodies to inhibit the interaction between immune checkpoint ligand (ICL) and receptor stimulatory receptor (CSR) augments T cell receptor (TCR) signaling initiated by the virus through (ICR), or with agonist antibody or expression of the co-stimulatory ligand (CSL) to bind with the presenting tumor-associated antigens (TAAs) with major histocompatibility complex (MHC), leading to enhanced T cell activation co-stimulatory receptor (CSR) augments T cell receptor (TCR) signaling initiated by the virus through against the tumor
With the approval of T-VEC for intratumoral therapy of non-resectable metastatic melanoma, oncolytic virotherapy starts to deliver its promise as an alternative therapy for cancers that are refractory to traditional chemotherapy, radiotherapy, targeted therapy, and immunotherapy
Summary
The history of cancer therapy is a witness of toxicity and failure of efficacy despite numerous efforts to identify druggable cancer targets for personalized and targeted treatments. To increase the efficacy in patients who are refractory to single antibody blockade, different immune checkpoint blocking antibodies have been combined to treat these patients [8,9] This may unavoidably increase the risk for irAEs. To pursue the specificity and safety of immunotherapy, efforts have been made to define cancer-associated antigens and develop therapeutic cancer vaccines. That is, during virotherapy, the in situ viral infection, replication, and subsequent tumor necrosis cooperate to disrupt immunosuppression within the tumor microenvironment, resulting in T cell reactivity against cancer neo-antigens [15,16,17] Taken together, it seems there could be an opportunity to take advantage of the above strategies to disrupt the immunosuppression within the tumor, upregulate the activity of tumor-specific T cell, and further develop more efficacious and safe therapies for cancer patients
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