Preclinical evaluation of a CCL19 immune-potentiated DNA cancer vaccine.

Plasmid DNA vectors are emerging as a versatile antigen delivery platform for personalized cancer vaccines. Here, we report a comprehensive preclinical evaluation of a modular DNA cancer vaccine that targets antigen-presenting cells and encodes tumor-specific antigens (TSAs), including neoantigens and endogenous retroviral (ERV) antigens. To specifically direct the TSAs to APCs, the chemokine C-C motif ligand 19 (CCL19) was incorporated, enhancing the magnitude and persistence of antigen-specific CD4+ and CD8+ T-cell responses. This resulted in strong anti-tumor activity in multiple murine models. Delivery via clinically relevant DNA methods, including electroporation and needle-free injection systems, further improved immune responses compared to standard syringe/needle injection. Pharmacokinetic and toxicological analyses of the CCL19 component demonstrated rapid systemic clearance and an absence of adverse effects, supporting its suitability for clinical application. The platform exhibited a favorable safety profile across repeated administrations at clinically relevant and escalated dosing regimens, including in combination with immune checkpoint blockade. Furthermore, in vitro and in vivo evaluation of multiple antigens confirmed consistent protein expression and sustained immunogenicity, irrespective of antigenic composition, underscoring the platform's robustness and translational potential for individualized cancer vaccine strategies. These findings demonstrate that the CCL19-targeted DNA vaccine platform is both immunologically potent and holds strong potential in personalized cancer therapy.