Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine

He Hu; Nicole F Steinmetz

doi:10.3390/cancers13122909

Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine

Cancers (Basel). 2021 Jun 10;13(12):2909. doi: 10.3390/cancers13122909.

Authors

He Hu¹, Nicole F Steinmetz^{1

2

3

4

5

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Affiliations

¹ Department of NanoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
² Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
³ Department of Radiology, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
⁴ Center for Nano Immuno-Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
⁵ Moores Cancer Center, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.
⁶ Institute for Materials Discovery and Design, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, USA.

Abstract

To develop a human epidermal growth factor receptor-2 (HER2)-specific cancer vaccine, using a plant virus-like particle (VLP) platform. Copper-free click chemistry and infusion encapsulation protocols were developed to prepare VLPs displaying the HER2-derived CH401 peptide epitope, with and without Toll-like receptor 9 (TLR9) agonists loaded into the interior cavity of the VLPs; Physalis mottle virus (PhMV)-based VLPs were used. After prime-boost immunization of BALB/c mice through subcutaneous administration of the vaccine candidates, sera were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) for the CH401-specific antibodies; Th1 vs. Th2 bias was determined by antibody subtyping and splenocyte assay. Efficacy was assessed by tumor challenge using DDHER2 tumor cells. We successful developed two VLP-based anti-HER2 vaccine candidates-PhMV-CH401 vs. CpG-PhMV-CH401; however, the addition of the CpG adjuvant did not confer additional immune priming. Both VLP-based vaccine candidates elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor growth was delayed, leading to prolonged survival of the vaccinated vs. naïve BALB/C mice. The PhMV-based anti-HER2 vaccine PhMV-CH401, demonstrated efficacy as an anti-HER2 cancer vaccine. Our studies highlight that VLPs derived from PhMV are a promising platform to develop cancer vaccines.

Keywords: CpG-ODN; HER2; breast cancer; cancer vaccine; virus-like particle.

Grants and funding

R01CA224605/CA/NCI NIH HHS/United States