Transdermal bicarbonate therapy increass intra-tumoral pH and elicits amti-tumor responses in bladder cancer

Methods

We show that acidity alters T cell proliferation, migration and effector functions as well as transcriptional programming using in vitro culture techniques and RNA sequencing. We then tested the potency of a proprietary transdermal formulation, DYV800, containing sodium bicarbonate to increase the extracellular tumor pH (pHe) and augment anti-tumor immune responses in a murine model of bladder cancer. The tumor pH was assessed using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI) and antitumor immune responses via flow cytometry.

Results: We found that transdermal DYV800 significantly reduced tumor burden and improved antigen-specific CD8+ T cell responses. Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI) of treated tumors showed an increase in intra-tumoral pH of bladder tumors, and this therapy also alkalizes the urine. Discussion/Conclusion: The transdermal delivery of DYV800 led to durable anti-tumor immune responses and is more clinically applicable to combat acidity in bladder cancer than oral bicarbonate.

Targeting acidosis in the bladder tumor microenvironment has the potential to enhance T cell responses and improve anti-tumor immunity.