Bone spread (metastasis) is a common complication arising from patients with advanced primary breast and prostate cancer which results in debilitating pain caused by fracture and nerve damage. Metastatic tumour cell clones which disseminate often have vastly different properties to the primary tumour, including reduced intrinsic immunogenicity. Existing immunotherapies are currently ineffective in the bone metastatic setting – owing to the tumours enhanced capacity to remain hidden from key immune cells whilst simultaneously hijacking key bone remodelling pathways. However, these therapies can be improved on in both the primary and metastatic setting with a more personalised approach, and this will be facilitated with developing effective ex vivo systems which can support patient tissue for interrogation. Our lab is currently working on two models which aim to support patient primary and metastatic tissue ex vivo – a sponge scaffold for breast and prostate tissue explants, and a bone bioscaffold for the seeding of patient bone metastatic cells. The bone bioscaffold originates from cow bone and can support the growth of patient bone met samples ex vivo for up to three weeks, facilitated by endogenous bone-ECM components which aid the cell’s engraftment and survival. These cells can be tracked via multiphoton microscopy and flushed for further interrogation via flow cytometry and genomics where their metastatic and immunogenic properties can be interrogated. Both systems are being optimised using syngeneic mouse models that allow interrogation of optimal conditions for maintaining tumour-immune cells interactions, and how biological and therapeutic alterations influence response to immunotherapies. Ultimately, this system will be utilised for human samples taken from neoadjuvant trials or at time of autopsy to act as a crucial pre-clinical screening tool to help create a paradigm of personalised immunotherapy. Together, these two preclinical models aim to advance our understanding of immunotherapies in the primary and metastatic setting.