Image-Guided Surgery (IGS) and Personalised Postoperative Immunotherapy to Improving Cancer Outcome

Despite progress in all the areas of cancer treatment, both in surgery, chemotherapy, radiation therapy and immune therapies, there is still a long way to consider that we are close to defeat this plague of the advanced societies. The importance of the immune system in the host response against cancer has been studied for many years. However, treatment of cancer by single immunotherapy has been proven to be only modestly effective. The aim of this project is to address the issues of postoperative immuno-modulation after Image-Guided Surgery (IGS) by means of nanoparticles-based encapsulated libraries of different immunotherapeutic biomolecules that are needed to improve cancer outcome. 

Surgery remains an effective treatment option for many types of cancer today and it is considered curative treatment for most solid tumors. It forms part of a multidisciplinary approach used in conjunction with radiotherapy or chemotherapy. These approaches, however, have several limitations, including inability of surgical resection to affect distal metastatic disease, toxicity to healthy tissues with chemotherapy and lack of effectiveness of radiation therapy in more aggressive tumors. The observation that cancer can relapse months or years after initial surgery implies that micrometastases still resides within the body in a latent state. Nanoparticles (NPs) are new concepts of treatment that allow encapsulate many different types of molecules, as: chemotherapeutic drugs, avoiding their free circulation and unspecific toxicity. They could be targeted to specific cells (e.g. cancer cells) precluding toxicity to healthy tissues and organs. At the same time, NPs permit to be loaded with dyes to identify tumor cells in distal points of the body or with tumor antigens, acting as vaccines or immunomodulatory molecules activating the immune response. Our approach will centre on a polymeric and biodegradable nanoparticles, degraded in the cells as physiological metabolites (no toxics), which is already FDA approved, but we will make structural changes, e.g. hydrophobicity, charge, molecular weight, to manipulate its adjuvant activity then monitor in vivo immune function such as T-cell activation and tumor regression in parallel and in dual colour. NP-based encapsulated libraries of different immunotherapeutic biomolecules, e.g. checkpoint blockade with a vaccine, will provide a versatile platform for this work. This means having the multiplex capability to target, to incorporate different immune components, based on a personalised approach of using specific molecular profiles derived from each patient, whereby combination immunotherapy will be implemented to optimally recruit the hosts’ own immune system to eradicate distal metastases and to image therapeutic efficacy.