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Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma.
- Source :
-
Scientific reports [Sci Rep] 2024 Oct 19; Vol. 14 (1), pp. 24545. Date of Electronic Publication: 2024 Oct 19. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Humans
Rats
Antigens, Neoplasm immunology
Antigens, Neoplasm genetics
Melanoma, Experimental immunology
Melanoma, Experimental therapy
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal therapeutic use
Antibodies, Monoclonal immunology
Cell Line, Tumor
Female
Disease Models, Animal
Lentivirus genetics
Melanoma therapy
Melanoma immunology
Melanoma drug therapy
Melanoma genetics
Mice, Inbred C57BL
Receptor, ErbB-2 metabolism
Receptor, ErbB-2 immunology
Receptor, ErbB-2 genetics
Receptor, ErbB-2 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39427012
- Full Text :
- https://doi.org/10.1038/s41598-024-76209-z