pHerapeutics: Modulating the tumour microenvironment restores immunosurveillance, eliminates cancer's "home-field" advantage, and potentiates therapies
Dr. John Trant
University of Windsor
FUNDER: Equally WE-SPARK Incentive Grant, Vice-President Research & Innovation (VPRI)
The ability of cells to evade detection and destruction by the immune system is a hallmark of cancer. Immunotherapy requires both overcoming the mechanisms by which cancer cells circumvent immune surveillance as well as re-sensitizing the tumour to inflammation, for example, training the immune system to recognize cancer-related antigens and making "invisible" cells visible to the immune system. There are multiple therapies being developed to address this challenge, including chimeric antigen receptor (CAR)-T-cell therapy, anticancer vaccines, and therapeutic antibodies. These therapies have only achieved limited success, with a major issue being the low (acidic) pH of the tumour microenvironment (TME), which is highly detrimental to immune cells, including T-cells, rendering them less effective. Published attempts to modulate the pH of TME by blocking proton pumps have been clinically ineffective. Through testing an enzymatically resistant, cancer-targeting, modulator based on carbohydrate imaging that restores physiological pH, this could potentiate other cancer therapies and resolve the issue around the pH of TME.
Through the successful modulation of the TME by controlling pH, this has the potential to restore the proper functions of the immune response at tumour sites while decreasing its metastatic potential and sensitizing the tumour to available therapies. This could lead to clinical trials against additional cancer indications and as a co-therapy with different treatments.