Towards improving cancer immunotherapy: development of novel antibody-based therapeutics and drug delivery systems

The human immune system is an integral network of cells, tissues, and organs that combats infections and foreign substances while maintaining homeostasis within the human body. Cancer immunotherapy aims to enhance the immune system's natural ability to fight cancer. For some previously untreatable patients, immunotherapy has led to prolonged complete remissions. Unfortunately, the response to immunotherapy has often been limited to a subset of patients, possibly due to the variation and complexity of cancer and the immune system in each individual. This thesis explores various avenues within the field of cancer immunotherapy to better understand what regulates the anti-cancer immune response and how it can be strengthened. Specifically, new immune targets, immunomedicines, and nanoparticles were investigated with the goal of improving the therapeutic efficacy of cancer immunotherapy. This led to the discovery that SIRP-β2 (a signal-regulating protein) is a positive regulator of innate immunity, where therapeutic activation could potentially enhance the anti-cancer immune response. Additionally, the new drug CD27xEGFR (a bispecific antibody) was successful in enhancing T-cell immunity in EGFR-positive cancer cells through targeted co-stimulation of CD27, in vitro. Furthermore, a new nanoparticle (vaterite nanoparticles) was developed, which can be used as a versatile drug delivery system for protein-based medicines that could have broad applications in cancer immunotherapy. Finally, an alternative technique was explored that may increase the maximum concentration of medicines in nanoparticles, potentially leading to better functioning nanomedicines.