Virus nanoparticle intratumoral vaccines for HER2+ malignancies.

Abstract

Our laboratory specializes in the intratumoral (i.t.) delivery of virus nanoparticles (VNPs) that activate immune cells and modulate the tumor microenvironment (TME). For this study, we conjugated the CH401 peptide-containing B-cell, helper T-cell, and cytotoxic T-cell epitopes of HER2-to the plant cowpea mosaic virus (CPMV) and bacteriophage Qβ to develop vaccines for HER2⁺ cancer. In vivo studies confirmed that the CPMV_CH401 i.t. therapeutic vaccine candidate was successful in CT26-HER2 and MC38-HER2 tumor models through the induction of IgG2a antibodies, upregulation of Th1 cytokines, and activation of Th1 cells. On the other hand, the Qβ_CH401 i.t. therapeutic vaccine candidate induced IgG1 antibodies and a Th1/2 balanced response, which did not result in potent anti-tumor efficacy. This study highlights that different VNP carriers are differential in immune modulation and that CPMV_CH401, but not Qβ_CH401, is effective as an i.t. vaccine. We also learned that the subcutaneous prophylactic immunization route leads to stronger humoral immunity but fails to modulate the TME, limiting the anti-tumor efficacy. This study highlights that, combined with the HER2 epitope, the i.t. therapeutic approach has powerful anti-tumor capabilities. It induces therapeutic HER2 antibodies, immunomodulation of the TME, and T-cell responses against the tumor, making this a robust active immunotherapy regimen.