(55d) Convection Enhanced Delivery of Light Responsive Antigen Capturing Oxygen Generators for Chemo-Phototherapy Triggered Adaptive Immunity

The growing scientific consensus on the poor effectiveness of monotherapies have led combination therapy to become one of the mainstay treatments in the war against cancer. However, it is essential to leverage on these combination therapies to trigger an adaptive immune response within the body to develop anti-tumoural immunity. In this work, we have developed light responsive antigen capturing oxygen generators (LAGs) which enables customizable payload release when subjected to light of 630 nm, and coverts the abundant hydrogen peroxide present in the cancer cells to oxygen using the grafted catalase. Furthermore, the maleimide groups allow the in-situ capture and retention of the released tumour antigens. We have conducted extensive material characterization to study the self-assembly of these LAGs in physiological conditions such as its particle size distribution, zeta potential, morphology, oxygen generation potential, and enzymatic efficacy. We then determined the route of cancer cell killing in 3D printed U87 spheroids. Co-localization assays suggested that the payloads were released predominately in the Golgi apparatus. LAGs downregulated the cell surface expression of CD86 costimulatory molecule and upregulated CD83 maturation marker on monocyte-derived dendritic cells. In the presence of 3D printed hypoxic spheroids, LAGs downregulated IL-10 and upregulated IL-1β, resulting in the proliferation of CD3+, helper CD4+ and cytotoxic CD8+.In contrast to conventional methods, our innovative approach exposes the immune system to a wide variety of TDPAs released through tumor cell death in a patient-specific manner. This treatment strategy could play a pivotal role in the advancement of personalized medicines.