Proceedings of the National Academy of Sciences of the United States of AmericaSep 2, 2026

Breast cancer prevention using a preventive Lalba mRNA nanoparticle vaccine

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Updated Sep 3, 2026

Abstract

Vaccination with LALBA mRNA-LNP suppressed carcinogen-induced mammary tumorigenesis and improved tumor-free and overall survival in rats.

Higher peripheral T cell diversity is associated with increased CD8⁺ T cell infiltration in early breast tumors.
Prophylactic vaccination against the LALBA protein may enhance immune response and contribute to tumor suppression.
Different formulations of LALBA mRNA-LNP elicited varying immune responses in vaccinated rats.
Vaccination was linked to a decrease in a specific population of proliferative cells in early-stage breast lesions.
No significant toxicity was observed in normal mammary glands or other organs following vaccination.

Simplified

Tumor-suppressive immunity is more evident in early-stage compared to advanced tumors making it the ideal point for cancer interceptive immunotherapies. We previously described that higher peripheral T cell diversity is associated with more pronounced CD8⁺ T cell infiltration in ductal carcinoma in situ of the breast, implying a close interaction between peripheral and intratumor immunity. Here, we developed lipid nanoparticle (LNP)-encapsulated messenger ribonucleic acid (mRNA) vaccines expressing the alpha-lactalbumin (LALBA) protein unique to mammary luminal progenitors (LPs) to test whether enhancing immune response by prophylactic vaccination against the putative cell-of-origin of breast cancer suppresses tumorigenesis. Vaccination of outbred Sprague-Dawley rats with N1-methylpseudouridine-modified or unmodified Lalba mRNA-LNP induced different degrees of LALBA-specific and nonspecific immune responses. The vaccination suppressed carcinogen-induced mammary tumorigenesis and improved tumor-free and overall survival without obvious toxicity in the normal mammary glands and other organs. Single-cell transcriptomic analysis revealed that vaccination decreases the frequency of a proliferative LP population in immunoreactive early epithelial hyperplasia. Overall, we provide proof of principle that prophylactic Lalba mRNA-LNP has the potential to suppress the initiation and progression of early breast neoplastic lesions.

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Breast cancer prevention using a preventive Lalba mRNA nanoparticle vaccine

Abstract

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