Macrophages and their interactions with oncolytic viruses.

Macrophages are a highly plastic cell type and exhibit a range of defensive and regulatory functions in normal physiology. Phagocytic macrophages play an important role in defending against virus infection and they provide an important barrier that can limit the delivery of therapeutic viruses from the injection to the tumour. Within tumours, macrophages generally adopt an immunosuppressive phenotype and are associated with poor clinical prognosis. However their plasticity also provides the opportunity for therapeutic 're-education' of tumour-associated macrophages (TAMs) to adopt an active anticancer role. Oncolytic viruses present the possibility for non-specific stimulation of TAMs, and also the option for tumour-targeted expression of cytokines chosen specifically to modulate macrophage activation.

Improved in vitro human tumor models for cancer gene therapy.

Developing effective anticancer treatments is a particular challenge, as agents must contend with not only the target cellular biology, but also with the complex tumor microenvironment. Here we discuss various in vitro strategies that have sought to address this issue, with a particular focus on new methodologies that utilize clinical samples in basic research and their application in gene therapy and virotherapy.