DNA vaccines have emerged as an attractive immunotherapeutic approach against infectious diseases and cancer due to its fast, efficient design and validation. It remains, however, a challenge in clinical settings due to historically low levels of immunogenicity in humans. In order to enhance the immunogenicity of DNA vaccines used as a cancer therapy, we have developed a nucleic acid platform, UNITE (UNiversal Intracellular Targeted Expression), which combines novel delivery methods and adjuvants which complement our lysosomal targeting technology. Fusing a tumor associated antigen (TAA) with the Lysosomal Associated Membrane Protein 1 (LAMP-1), we can activate Ag specific CD4+ T cells by targeting the major histocompatibility complex II compartment. In this study, we selected ErbB2/Her2 as the cancer target because it is a broadly overexpressed and well-characterized oncoantigen.

Mice vaccinated with Her2-LAMP DNA demonstrate robust Her2-specific CD4+ and CD8+ T cells, in addition to antibody responses, which in turn have significant antitumor effect in murine breast and bladder tumor models. Moreover, we demonstrate that the Her2-LAMP vaccine promotes CD8+ T cell tumor infiltration to a greater degree than when compared to a traditional DNA vaccine without LAMP. In summary, we show that UNITE as a nucleic acid platform, can enhance antitumor immunity in vivo.

Citation Format: Renhuan Xu, Teri Heiland. DNA vaccine co-expressing Her2/ErbB2 antigen, fused with LAMP, elicits strong antitumor effects in vivo by increasing tumor infiltration with CD8+ T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-204.