Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice
 
The importance of having a versatile immunotherapeutic approach with new combination strategies means that we would need to use biomaterials for this task. These serve a multitude of roles and may act as carriers, be targeted and modified to being able to act as adjuvants for vaccines. In WP4, we will investigate two routes of delivery (local and systemic) of immunomodulatory reagents on a biomaterial vehicle and a route of delivery for an oncolytic virus to target monocytes and TAMs. The MP will be used for local delivery of immune components whilst the NP will be used for systemic delivery where the components need to be targeted to circulating and tissue-resident cells in vivo. A defined biomaterials-based library of immunotherapeutic combinations (a complementary list has been provided in section for in case the expert reviewers would like to consult it) will be one of the deliverables. Furthermore, the particle format will also be able to accommodate optical or MRI tracking to enable monitoring of immune function. Survival (outcome) studies using mouse models will be performed to monitor the efficiency of the different immunotherapy strategies. We have designed a new form of virotherapy which currently uses ex vivo manipulated MQs to deliver large quantities of a hypoxia-inducible factor (HIF-) regulated oncolytic adenovirus to hypoxic areas of primary human prostate tumours and their pulmonary metastases in mice (11). When released byMQs in tumours, the virus undergoes further amplification in tumour cells under the control of a prostate-specific promoter sequence. This results in widespread lysis of tumour cells and markedly inhibits subsequent tumour growth and metastasis. However, the ex vivo transfection of macrophages with the virus is not feasible in a clinical setting.

Our 2 objectives are, therefore, as follows:
4.1. To combine different immunological payloads and an imaging modality on the biomaterial platform for maximal immunotherapeutic efficacy,
4.2. NP-targeted oncolytic viral delivery to monocytes in circulation (in vivo) which therefore circumvents the need for ex vivo infection of these cells prior to reinfusion back into the patient. This will greatly simplify this new oncolytic therapy.

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