PhD defence M. (Mesha) Saeed

Summary:

Cancer therapies have been widely studied and constant efforts and measures to develop better therapies are in action. Recently, immunotherapy has yielded significant treatment effects in a range of cancers. Interestingly, melanoma represents a prime target for immunotherapy due to the expression of certain antigens on the cell surface, the intrinsic immunoresponsive nature of the disease and easy access of the primary tumor. In my thesis, I have looked at the selection of melanoma antigen-specific antibodies via Phage Display technique. Previously selected antibodies were used as targeting moieties to develop smart nanoparticles which we coined as immune Smart Drug Delivery Systems (iSDDS) that target melanoma (as a tumor model) and show that by combining these nanoparticles with drugs, it was possible to successfully deliver chemotherapy on site effectively. Our lipid based nanoparticles were combined with antibodies, specific to melanoma antigens that were recognized in a TCR-like manner. These smart nanoparticles ensured safe and on-target delivery of the cargo such as chemotherapeutic drugs that were entrapped. I propose that with the selection of these new antibodies, a vast spectrum of melanoma antigens can be targeted according to iSDDS. This thesis describes the selection of new antibodies, production and characterization of pre-selected antibodies, development of iSDDS, and their characterization, in vivo efficacy, evaluation and delineation of future perspectives of these smart
nanoparticles. We conclude that iSDDS can be a platform that can be further enhanced and improved to transport immunomodulatory or immune-activating agents to tumors specifically and may well form the basis for combination therapies or vaccination. At the end, we discuss our research and compare it with
other studies and some future lines of this research.