Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 Oct 2024
19 Oct 2024
Historique:
received:
01
03
2024
accepted:
11
10
2024
medline:
20
10
2024
pubmed:
20
10
2024
entrez:
19
10
2024
Statut:
epublish
Résumé
In this study, we tested a novel approach of "repurposing" a biomarker typically associated with breast cancer for use in melanoma. HER2/neu is a well characterized biomarker in breast cancer for which effective anti-HER2/neu therapies are readily available. We constructed a lentivirus encoding c-erb-B2, an animal (rat) homolog to HER2/neu. This was used to transfect B16 melanoma in vitro for use in an orthotopic preclinical mouse model, which resulted in expression of rat c-erb-B2 as a neoantigen target for anti-c-erb-B2 monoclonal antibody (7.16.4). The c-erb-B2-expressing melanoma was designated B16/neu. 7.16.4 produced statistically significant in vivo anti-tumor responses against B16/neu. This effect was mediated by NK-cell antibody-dependent cell-mediated cytotoxicity. To further model human melanoma (which expresses < 5% HER2/neu), our c-erb-B2 encoding lentivirus was used to inoculate naïve (wild-type) B16 tumors in vivo, resulting in successful c-erb-B2 expression. When combined with 7.16.4, anti-tumor responses were again demonstrated where approximately 40% of mice treated with c-erb-B2 lentivirus and 7.16.4 achieved complete clinical response and long-term survival. For the first time, we demonstrated a novel strategy to repurpose c-erb-B2 as a neoantigen target for melanoma. Our findings are particularly significant in the contemporary setting where newer anti-HER2/neu antibody-drug therapies have shown increased efficacy.
Identifiants
pubmed: 39427012
doi: 10.1038/s41598-024-76209-z
pii: 10.1038/s41598-024-76209-z
doi:
Substances chimiques
Receptor, ErbB-2
EC 2.7.10.1
Antigens, Neoplasm
0
Antibodies, Monoclonal
0
Erbb2 protein, rat
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24545Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002379
Pays : United States
Informations de copyright
© 2024. The Author(s).
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