Abstract
Oncolytic viruses (OVs) are being extensively studied for their potential roles in the development of cancer therapy regimens. In addition to their direct lytic effects, OVs can initiate and drive systemic antitumor immunity indirectly via release of tumor antigen, as well as by encoding and delivering immunostimulatory molecules. This combination makes them an effective platform for the development of immunotherapeutic strategies beyond their primary lytic function. Engineering the viruses to also express tumor-associated antigens (TAAs) allows them to simultaneously serve as therapeutic vaccines, targeting and amplifying an immune response to TAAs. Our group and others have shown that vaccinating intratumorally with a poxvirus that encodes TAAs, in addition to immune stimulatory molecules, can modulate the tumor microenvironment, overcome immune inhibitory pathways, and drive both local and systemic tumor specific immune responses.
Highlights
Oncolytic viruses (OVs) are a family of viruses characterized by their preferential replication in—and subsequent lysis of—tumor cells following in vivo injection/trafficking to the site of the tumor
While there are a variety of different OVs actively being researched and developed for treatment, this review will focus primarily on the cancer therapeutic potential of poxviruses, especially vaccinia and fowlpox viruses, with recombinant expression of immunostimulatory molecules and tumor-associated antigens (TAAs) and in particular their ability to modulate the immune tumor microenvironment
Tumors recruit and activate immunosuppressive cell populations including T-regulatory cells (Tregs), myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and tumor-associated neutrophils, which can protect the tumor from a functional anti-tumor immune response [44,45,46,47]
Summary
Oncolytic viruses (OVs) are a family of viruses characterized by their preferential replication in—and subsequent lysis of—tumor cells following in vivo injection/trafficking to the site of the tumor. It soon became apparent that OV therapy can induce and enhance a systemic anti-tumor immune response, protecting treated mice from tumor re-challenge [4]. This created a rapidly growing field of OV-based cancer immunotherapy as researchers sought to harness the immune-enhancing capabilities of OVs. The advent of recombinant technology has allowed the development of OVs as vectors for gene therapy, encoding molecules to directly modulate immune responses. While there are a variety of different OVs actively being researched and developed for treatment, this review will focus primarily on the cancer therapeutic potential of poxviruses, especially vaccinia and fowlpox viruses, with recombinant expression of immunostimulatory molecules and tumor-associated antigens (TAAs) and in particular their ability to modulate the immune tumor microenvironment.
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