Engineering neoantigens to form immunogenic biopolymer particles targeting metastatic breast cancer

Cancer vaccines that target tumor-specific neoantigens have shown promising results in recent clinical trials. However, these vaccines are still in the early stages of development and face significant challenges, including fighting heterogeneous tumors, high costs and limited efficacy, restricting their accessibility to cancer patients. To overcome these challenges, we developed particulate neoantigen formulations by engineering Escherichia coli to assemble biopolymer particles (BPs) coated with neoantigens of interest facilitating effective uptake by antigen presenting cells and induction of neoantigen-specific immune responses. We designed, manufactured, and tested the therapeutic efficacy of BPs coated with retroviral glycoprotein 70-derived neoantigens in the 4T1 murine metastatic breast cancer model. Neoantigen-BP vaccine formulations were safe and effectively reduced tumor progression by enhancing the infiltration of cytotoxic and helper T cells into the tumor microenvironment. Tumor- infiltrating T cells displayed reduced levels of the immune suppressor marker B and T lymphocyte attenuator, while expressing higher levels of the death ligand FasL. This was aligned with neoantigen-BP vaccinated mice developing significantly lower numbers of tumors nodules in the lungs indicating immune response-mediated suppression of metastasis. Histological analysis showed more extensive necrosis in cancer tissues of vaccinated groups compared to control groups. The addition of immune chekpoint inhibitor, anti-PD1, had synergistic effects on tumor suppression. Overall, these findings support the feasibility of utilizing neoantigen-coated BPs as innovative neoantigen delivery platform to induce anti-tumor immune responses, mediating suppression of tumor progression.