Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine
| dc.contributor.author | Hu, He | en |
| dc.contributor.author | Steinmetz, Nicole F. | en |
| dc.contributor.department | Biological Systems Engineering | en |
| dc.date.accessioned | 2021-06-10T19:34:23Z | en |
| dc.date.available | 2021-06-10T19:34:23Z | en |
| dc.date.issued | 2021-06-10 | en |
| dc.date.updated | 2021-06-10T13:47:52Z | en |
| dc.description.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. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Hu, H.; Steinmetz, N.F. Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine. Cancers 2021, 13, 2909. | en |
| dc.identifier.doi | https://doi.org/10.3390/cancers13122909 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/103758 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | virus-like particle | en |
| dc.subject | cancer vaccine | en |
| dc.subject | HER2 | en |
| dc.subject | CpG-ODN | en |
| dc.subject | breast cancer | en |
| dc.title | Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine | en |
| dc.title.serial | Cancers | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |
| dc.type.dcmitype | StillImage | en |