预防性Lalba mRNA-LNP疫苗预防乳腺癌
Breast cancer prevention by prophylactic Lalba mRNA-LNP vaccination
乳腺癌若能在癌前阶段干预，免疫系统可能更有效。研究者开发了脂质纳米颗粒包裹的mRNA疫苗，表达乳腺管腔祖细胞特有的α-乳白蛋白（LALBA），针对乳腺癌可能的细胞起源进行预防性接种。在远交系Sprague-Dawley大鼠中，N1-甲基假尿苷修饰或未修饰的Lalba mRNA-LNP诱导了不同程度的LALBA特异性和非特异性免疫应答，抑制了致癌物诱导的乳腺肿瘤发生，改善了无瘤生存和总生存，且正常乳腺及其他器官未见明显毒性。单细胞转录组分析显示接种减少了免疫反应性早期上皮增生中的增殖性祖细胞群。
为什么推荐给您：癌症预防性mRNA疫苗的概念验证，靶点新颖但仅动物数据，属值得关注
不需要生物学背景，多打比方
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摘要Abstract
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.