Generating Primary Models of Human Cancer to Aid in the Development of Clinically Relevant Oncolytic Viruses

Oncolytic viruses (OVs) represent a rapidly advancing class of cancer immunotherapeutic that is helping to shift the treatment paradigm of cancer. Initially thought to only have direct oncolysis ability, the established anticancer mechanisms of action of OVs have rapidly expanded to incorporate a multitude of immune-activating properties. Specifically, the field is focused on harnessing OVs to train patients' immune systems to recognize and eradicate cancer. Recent scientific progress has enabled the shift in focus to clinical translation, and as such it has become increasingly important to utilize clinically relevant models in the development and testing of novel OVs. As a result of this need, some research groups have developed their own experimental models derived from clinical or surgical specimens at their home institutions. This chapter outlines methodology for the generation of three distinct patient-derived experimental models. This includes cell cultures derived from (1) malignant ascites of ovarian cancer patients, (2) direct excision of metastatic melanoma, and (3) core biopsies of pancreatic cancer. Each of these methodologies has been utilized to generate replicating cellular models and have been demonstrated as valuable tools in in vitro, in vivo, and ex vivo studies.