Prophylactic Lalba mRNA-LNP vaccination prevents the progression of early breast lesions
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ABSTRACT: We hypothesized that prophylactic vaccination targeting the potential cell-of-origin of breast cancer may contribute to the suppression of early tumorigenesis. Here, we developed lipid nanoparticle (LNP)-encapsulated mRNA vaccines expressing the alpha-lactalbumin (LALBA) protein unique to mammary luminal progenitors/alveolar-like cells. Vaccination of outbred Sprague-Dawley rats with N1-methylpseudouridine-modified or unmodified Lalba mRNA-LNP induced different degrees of LALBA-specific and non-specific immune response. While the vaccination caused no detectable toxicity in normal mammary glands or other organs, it suppressed Nitroso-N-methylurea (NMU)-induced tumorigenesis and enhanced the tumor-free survival. Single-cell transcriptomic analysis revealed that vaccination leads to the reduction of a distinct proliferative luminal progenitor population in immunoreactive early lesions. Overall, we demonstrated that prophylactic use of Lalba mRNA-LNP has the potential to suppress the initiation and progression of early breast lesions.
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE300205 | GEO | 2026/08/20
REPOSITORIES: GEO
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