Unleashing Systemic Anti-Tumor Responses: The Potential of AST-008 in Cancer Immunotherapy

Spherical nucleic acids (SNAs), which are liposomal nanoparticles with densely packed oligonucleotides arranged in a 3D structure, have shown to enhance cellular uptake and resist nuclease degradation. AST-008, a TLR9 agonist in SNA form, has been found to stimulate robust Th1 immune responses in laboratory settings and in animals. It has demonstrated significant antitumor effects when administered via subcutaneous, intratumoral, or intravenous routes, and has also amplified the effects of checkpoint inhibitors in various mouse cancer models. Prior research indicates that AST-008 can trigger strong innate and adaptive immune reactions, leading to an increase in tumor-infiltrating lymphocytes and activation of CD8+ T-cells, which in turn reduces T-regulatory cells in the tumor environment and enhances the efficacy of checkpoint inhibitors.

In the latest studies, the effects of AST-008 were examined through different administration methods in various tumor models. In the EMT-6 breast cancer model, subcutaneous delivery of AST-008 resulted in a dose-dependent decrease in tumor growth, which was statistically significant when compared to control groups. A control oligonucleotide-SNA did not affect tumor growth. In a two-flank EMT-6 model, the subcutaneous administration of the TLR9 agonist SNA led to substantial tumor growth inhibition at both the injected and non-injected sites. In the MC38 colon cancer model, AST-008 administered either subcutaneously or intratumorally induced a significant reduction in tumor size at the treated site, and also resulted in substantial tumor growth inhibition in distant, untreated tumors.

These findings highlight the sequence-specific antitumor capabilities of AST-008 and its potential to induce systemic antitumor effects when administered at a single tumor site. The results, in conjunction with previous studies on the combination of AST-008 with checkpoint inhibitors, suggest that AST-008 could be a valuable asset in cancer treatment, particularly when used in conjunction with checkpoint inhibitors. AST-008 is currently undergoing clinical development.