Chemical modulators of immune checkpoints and cell growth for cancer treatment

Unmet Need

Each year there are over 1.6 million new cases of cancer in the US, and over 600,000 cases prove fatal. Treating various types of cancer can be particularly challenging because of the complex biological processes that allow cancer cells to flourish and multiply despite harsh biological conditions. Additionally, many cancer cells produce proteins that deactivate immune cells that would otherwise detect the abnormal cells and destroy them. The proliferative ability of cancer cells, combined with their ability to disguise themselves from the immune system, makes them extremely difficult to eradicate. Therefore, there is a need for treatments that can address the wide variety of survival mechanisms that cancer cells use to persist in the body.

Technology

Duke inventors have developed a suite of several classes of chemical modulators of key signaling pathways related to cancer cell growth and immune detection. These molecules are intended to be used as anti-cancer therapeutics, either alone or in combination with a biologic cancer treatment such as cellular therapy or immunotherapy. Specifically, one class of molecules interferes with the Wnt/β-catenin pathway, directly inhibiting cancer cell growth. Another class stops cancer cells from presenting proteins that deactivate cancer-targeting T-cells, including PDL-1, thereby re-activating the immune system to attack tumors in the process. Researchers have demonstrated successful delivery of these molecules to the bloodstream after oral administration in animal experiments. Experiments in cultured human cells and patient tumor explants grown in mice demonstrated successful cellular uptake of the molecules and confirmed their anti-cancer activity. Specifically, the authors have demonstrated that the various classes of molecules successfully slow cancer cell growth and restore T-cell activity in animal models and in human cells.

Other Applications

This technology would be well suited for cancer applications such as colorectal cancer, melanoma, lymphoma, pancreatic cancer, multiple myeloma, prostate cancer, renal cell carcinoma, bladder cancer, and non-small cell lung cancer. These molecules also demonstrate antiviral and antibacterial activity, and have additional applications related to lupus, type II diabetes, nonalcoholic steatohepatitis (NASH), and nonalcoholic fatty liver disease (NAFLD).

Advantages

• Small-molecule nature of technology means there is a lower cost of development and manufacturing, better volume distribution, fewer inflammatory side effects, and easier patient administration than biologic treatments.
• Can be combined with a biologic therapy to increase beneficial effects of overall treatment.
• Suite of molecules targets multiple distinct cancer cell survival mechanisms.