Development of a salt-based nanomedicine for non-muscle invasive bladder cancer

摘要

Abstract Bladder cancer comprises 7% of new cancer diagnoses in the US. It is the sixth most prevalent malignancy, and has the highest lifetime treatment costs among all cancer types due to the need for lifelong surveillance. Early stage bladder cancer, also known as non-muscle-invasive bladder cancer (NMIBC), represents 75% of new bladder cancer cases. The standard treatment is transurethral resection of bladder tumor (TURBT), followed by intravescical therapy with chemotherapeutics such as mitomycin C or Bacille Calmette-Guérin (BCG). However, ~30% patients are refractory to BCG. Chemotherapies are assocaited with relatively high recurrence rates and ineffective as a second-line treatment for patients unresponsive to BCG. Meanwhile, no new intravesical drugs have been approved since 1998. There is an unmet clinical need for new NMIBC therapies. Athna Biotech, Inc. is developing a sodium chloride nanoparticle (SCNP) based cancer therapeutic. SCNPs deliver large amounts of Na+ and Cl- into cancer cells, by doing so disrupts the osmotic balance across the plasma membrane. Uniquely, SCNPs induce immunogenic cell death or ICD. This means that SCNPs essentially produce a vaccine in situ out of dying cancer cells, eliciting an antitumor immunity that prevents tumor recurrence and progression. SCNPs are intravesically instilled into the affected bladder to kill residual cancer cells after TURBT. After the treatment, SCNPs degrade to constitute ions that are excreted in the urine. The procedure is safe and can be applied repeatedly without causing local or systemic toxicity. In Phase I, we will test the efficacy of SCNPs in a mouse orthotopic bladder cancer model. In Phase II, we will evaluate the efficacy of SCNPs in an expanded pre-clinical study and perform IND-enabling pharmacokinetics and toxicity studies.