Nanomedical systems: from the clinical trial to the certification of a medical device for off-label usage and related use of nanoparticles for anticancer therapy

Extracorporeal photopheresis (ECP) is a therapy currently used to treat some types of cancer, including cutaneous T-cell lymphoma (CTCL), a rare malignancy of the lymphatic tissue that involves the abnormal proliferation of T lymphocytes in the skin. This therapy consists in taking lymphocytes which, after being treated with photo responsive drugs activated by UVA light, are reinfused into the patient where they generate a response from the immune system which consequently regulates itself to kill cancer cells. Although the ECP has been a technology applied for more than 25 years to treat different kinds of diseases, the mode of action of the therapy remains still unknown and it is thought to be mainly attributable to an immunomodulatory effect that originates when the treated lymphocytes are reintroduced inside the patient. Starting from the present technology, an attempt was first made to investigate, from the available literature, the main theories advanced on the ECP mode of action and then to underline the related benefits and limitations. In particular, trying to overcome the main limitations of ECP, an experimental study is under development between the group of Prof. Cauda (Politecnico di Torino) in collaboration with the San Lazzaro Dermatological Hospital of Turin in which an alternative procedure, similar to ECP one, is being introduced. Nanoparticles, suitably formulated to present maximum biocompatibility and in vivo stability, are added in non-cytotoxic doses to lymphocytes taken from CTCL patient and activated using ultrasound as an external stimulus and no longer UVA light as in the traditional ECP. The purpose of this thesis arises downstream of the aforementioned experimental clinical study and it is divided into different parts. At first, the software used for the collection and statistical analysis of clinical data (REDCap) is studied, highlighting its main functions and strengths. Subsequently, attention is focused on the medical device used for the delivery of ultrasounds (Intelect Mobile 2 ULTRASOUND) currently certified for physiotherapy uses. The fundamental steps to be followed to obtain the CE certification for the off-label use of the device are proposed in the experimental study, applying the current legislation on medical devices (EU Regulation 2017/745). Lastly, in order to understand the next steps to be followed to certify nanoparticles so that they can be used in clinics, several clinical trials are analyzed, in which different nanoparticles, activated by a variety of external stimuli, have been involved, to cause cancer cells death.