Targeted Therapy of Melanoma using Smart Drug Delivery Systems

Previously known treatments for cancer included surgical removal of the tumor followed by radiotherapy and chemotherapy. However, chemotherapy often led to enhanced toxicity and patients experienced serious side effects from the treatment. 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. 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 deploy several assays for characterization of antibodies, pre and post coupling to the nanoparticles, SDS, ELISA and Flow Cytometry with native cells are examples. We show that targeted liposomes using TCR-like antibodies against melanoma are used as principal system to transport drug to melanoma tumors in vivo. It is demonstrated that our iSDDS are effective and specific towards melanoma tumors and are able to transport and release the drug at tumor sites or in vicinity. 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.