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Article

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

by 1 and 1,2,3,4,5,6,*
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
*
Author to whom correspondence should be addressed.
Academic Editor: Tatjana Paunesku
Cancers 2021, 13(12), 2909; https://doi.org/10.3390/cancers13122909
Received: 27 April 2021 / Revised: 21 May 2021 / Accepted: 7 June 2021 / Published: 10 June 2021
Virus-like particles (VLPs) have attracted significant interest as immunotherapy platforms and cancer vaccines for inducing antigen-specific immune responses against tumors. We prepared a human epidermal growth factor receptor-2 (HER2) cancer vaccine, by conjugating the HER2-derived CH401 epitope to the external surface of Physalis mottle virus (PhMV)-like particles via copper-free click chemistry. Another candidate was prepared by loading Toll-like receptor 9 (TLR9) agonists as adjuvant into the interior cavity of PhMV-CH401—although the addition of the adjuvant conferred no additional immune priming. The VLP-based anti-HER2 vaccine candidate was administered subcutaneously, using a prime-boost immunization schedule and BALB/c mice. The vaccine candidate elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased the toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor challenge studies demonstrated efficacy, as evident from the delayed onset of tumor growth and the prolonged survival of the vaccinated vs. naïve BALB/C mice.
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. View Full-Text
Keywords: virus-like particle; cancer vaccine; HER2; CpG-ODN; breast cancer virus-like particle; cancer vaccine; HER2; CpG-ODN; breast cancer
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MDPI and ACS Style

Hu, H.; Steinmetz, N.F. Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine. Cancers 2021, 13, 2909. https://doi.org/10.3390/cancers13122909

AMA Style

Hu H, Steinmetz NF. Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine. Cancers. 2021; 13(12):2909. https://doi.org/10.3390/cancers13122909

Chicago/Turabian Style

Hu, He, and Nicole F. Steinmetz. 2021. "Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine" Cancers 13, no. 12: 2909. https://doi.org/10.3390/cancers13122909

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