Heterologous Prime-Boost Immunization of AAV-based Neoantigen Cancer Vaccine Induces Anti-Tumor Immunity to Inhibit Tumor Growth and Relapse

Our previous work developed a novel engineered adenovirus-associated virus (AAV)-based tumor-specific (neoantigen) cancer vaccine to boost antitumor immunity in combination with radiotherapy, resulting in tumor regression and less distant metastasis. However, the therapeutic efficacy of constitutive vector-based vaccination may be limited by poor immunogenicity, pre-existing vector-specific immunity, and vaccine-induced vector-specific immunity.

Here, we examined the combinational therapeutic efficacy of AAV-based cancer vaccine, local radiotherapy and immune checkpoint blockade (ICB) in two poor immunogenic cancer animal models. We found that administration with AAV-based neoantigen vaccine significantly increased the response to radiotherapy and ICB, and decreased the risk of distant metastasis. Furthermore, we evaluated a heterologous prime-boost immunization strategy using two optimized AAV serotype vaccines to amplify tumor-specific immunity to neoantigens.