Grant: CIHR Fellowship

According to the Canadian Cancer Statistics, it was estimated that there were 206,000 cancer diagnoses and 80,800 cancer-related deaths in 2017 across the nation. One of the hallmarks of cancers that make them resistant to therapy is their ability to evade the host immune system. Some cancers express a protein called programmed death-ligand 1 (PD-L1) that can suppress or 'turn off' a patient's immune response. When this happens, the T-cells in our body which are responsible for destroying harmful cells become less active. By pharmacologically inhibiting PD-L1, oncologists can stimulate a patient's own immune system to help combat cancer. This strategy has proven to be effective for skin and lung cancers patients; however, there are many patients who do not derive benefit from treatment. One way to improve efficacy is by combining anti-PD-L1 inhibitors with other treatment modalities like radiation therapy. In this project, we will label a novel class of anti-PD-L1 inhibitors with therapeutic radioisotopes for the bimodal treatment of cancer. In the first part of our proposal, we will use positron emission tomography (PET) as an imaging modality to screen and identify potent anti-PD-L1 inhibitors. In the clinic, PET is used routinely for cancer diagnosis, staging and monitoring treatment response. PET can also accelerate the drug development process by enabling visualization of drug accumulation in tumours and normal tissues. In part two, we will assess the ability of the anti-PD-L1 inhibitors to target tumours in combination with radiotherapy using various animal cancer models. We will measure the survival of our animal models and determine any treatment-associated toxicity. The success of this project will lead to new therapeutic agents that can alleviate immune suppression and concomitantly deliver lethal radiation to cancer cells, thereby improving cancer patient outcomes.