Targeting Bladder Cancer with DPX-SurMAGE: Preclinical Insights into a Dual-Targeted Immunotherapy

A significant portion of high-risk non-muscle invasive bladder cancer (NMIBC) cases do not respond to conventional treatments, prompting the need for alternative therapies to avoid radical cystectomy. The DPX platform offers an innovative solution, utilizing a lipid-based system to deliver a variety of biological molecules to antigen-presenting cells (APCs), which can trigger a focused and enduring immune reaction. Maveropepimut-S (MVP-S), a DPX-based immunotherapy, has shown to stimulate a survivin-specific immune response with minimal side effects in cancer patients.

Survivin and MAGE-A9 are tumor-associated antigens (TAAs) that are often overexpressed in bladder cancer. A new immunotherapy, DPX-SurMAGE, has been developed using the DPX platform to target both survivin and MAGE-A9 with HLA-A2 restricted peptides. Studies in HLA-A2 transgenic mice have shown that DPX-SurMAGE can elicit similar T cell responses against survivin as MVP-S, indicating that the addition of MAGE-A9 peptides does not diminish the effectiveness of the survivin-specific response.

Further evaluations of DPX-SurMAGE with and without metronomic cyclophosphamide (mCPA) have demonstrated potent induction of T cell responses against both survivin and MAGE-A9 peptides, with sustained responses throughout the long-term phase of testing. Preliminary safety assessments revealed no signs of toxicity or significant weight changes in treated mice, and injection site reactions were comparable to a control group.

This research underscores the DPX platform's capability to deliver multiple antigenic peptides without reducing their immunogenicity. DPX-SurMAGE has proven to be well-tolerated and capable of inducing strong, sustained T cell responses against both targeted antigens, providing a promising foundation for an upcoming phase 1 clinical trial for high-risk NMIBC patients.