Grant: Project Grant

Skin cancer is the most common cancer in Canada. In 2022, there were 197,700 new cases of melanoma diagnosed and 7,650 deaths resulted from the disease. If diagnosed early, melanoma has a high chance of cure, and with the recent Health Canada approval of anti-cancer antibodies, the overall survival rate at 5 years for advanced melanoma has significantly increased. However, the complex tumor environment in late-stage metastatic melanoma makes it extremely challenging to treat unresponsive patients to currently approved drugs. Several factors are involved in melanoma's resistance to treatment, including a significant reduction in the cancer's drug sensitivity and a lack of tumor-killing immune cells. Previous research has shown that certain bacteria can preferentially accumulate in tumors and activate the immune system against the disease. So far, bacteria alone have been ineffective in generating an immune response strong enough to reduce tumor growth in melanoma's patients. We recently demonstrated that nanoparticles loaded with two anti-melanoma drugs called 6-bromo-indirubin-3'-oxime (6BIO) with the copper chelate diethyldithiocarbamate (CuET) can be formulated alongside tumor-targeting bacteria to enhance the immune response. We identified a non-toxic bacterium called MSR-1 that could target tumors and activate the immune system. Our preliminary results show that MSR-1 is well tolerated in mice, and when given to tumor-bearing mice, it significantly reduces tumor growth and improves survival without causing major toxicity. Thus, our goal is to engineer bacterial nanoplexes containing 6BIO and CuET as a treatment modality for melanoma patients who are unresponsive to current immunotherapies. Our preliminary results stipulate that the nanoplexes containing 6BIO and CuET alongside MSR-1 bacteria will act synergistically and generate a strong immune response against melanoma, potentially improving the clinical outcomes for patients with no other therapeutic options.