Project #5

SPHERICAL NUCLEIC ACIDS AS MULTIANTIGEN IMMUNOTHERAPEUTIC VACCINES

Prof. Chad A. Mirkin
Prof. Alexander Stegh

Immunotherapy is a powerful emerging treatment for a variety of malignancies. Specifically, the use of cancer vaccines within the field of immunotherapy has revitalized interest in potentiating targeted antitumor immune responses. Using an immune system activator and an immune system target, these vaccines can drive the immune system to seek out and kill tumor cells.

Spherical nucleic acids (SNAs), nanostructures that are now part of four human clinical trials, take advantage of structure-activity relationships to press the immune system’s “gas pedal” and deliver the appropriate antigen for cancer immunotherapy.

We present two new strategies for strengthening antitumor immune responses that target more than one peptide antigen sequence or protein, to hasten the clinical translation of these nanostructures for treatment of metastatic castrate-resistant prostate cancer (mCRPC). We seek to induce responses towards a broad variety of prostate cancer (PCa) specific immunogenic peptides. To do this, we propose to design an SNA vaccine capable of delivering multiple epitopes. We will also utilize a new class of SNA, the protein SNA (ProSNA), where the core is a PCa tumor-associated protein, as a vaccine.

By enhancing the delivery of whole tumor-associated proteins to antigen-presenting cells, we will enable the cells to develop antigens internally which can elicit broader and more potent antitumor immune responses. The pursuit of these strategies will contribute to rational vaccine design, and their investigation in both transgenic mouse tumor models and human PCa patient samples will allow for facile clinical translation. This new project is funded in part by a Polsky Urologic Cancer Institute Research Award.