文章：

一种新型鼻内肽疫苗可抑制KRAS突变的非小细胞肺癌

A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation 

原文发布日期：2024-01-04 

英文摘要：

KRAS mutations occur commonly in the lung and can lead to the development of non-small cell lung cancer (NSCLC). While the mutated KRAS protein is a neoantigen, it usually does not generate an effective anti-tumor immune response on mucosal/epithelial surfaces. Despite this, mutated KRAS remains a potential target for immunotherapy since immune targeting of this protein in animal models has been effective at eliminating tumor cells. We attempted to develop a KRAS vaccine using mutated and wild-type KRAS peptides in combination with a nanoemulsion (NE) adjuvant. The efficacy of this approach was tested in an inducible mutant KRAS-mouse lung tumor model. Animals were immunized intranasally using NE with KRAS peptides. These animals had decreased CD4+FoxP3+ T cells in both lymph nodes and spleen. Immunized animals also showed higher IFN-γ and IL-17a levels to mutated KRAS that were produced by CD8+ T cells and enhancement in KRAS-specific Th1 and Th17 responses that persisted for 3 months after the last vaccination. Importantly, the immunized animals had significantly decreased tumor incidence compared to control animals. In conclusion, a mucosal approach to KRAS vaccination demonstrated the ability to induce local KRAS-specific immune responses in the lung and resulted in reduced tumor incidence. 

摘要翻译： 

KRAS突变常见于肺部，并可导致非小细胞肺癌（NSCLC）的发生。虽然突变的KRAS蛋白是一种新抗原，但它通常不会在黏膜/上皮表面引发有效的抗肿瘤免疫反应。尽管如此，突变KRAS仍是免疫治疗的潜在靶点，因为在动物模型中对该蛋白的免疫靶向已能有效清除肿瘤细胞。我们尝试利用突变型和野生型KRAS多肽联合纳米乳佐剂（NE）开发KRAS疫苗。该方法在诱导性突变KRAS小鼠肺肿瘤模型中进行了效果测试。通过鼻内接种方式给动物免疫NE与KRAS多肽复合制剂，发现这些动物淋巴结和脾脏中的CD4+FoxP3+ T细胞均减少。免疫动物还表现出由CD8+ T细胞产生的针对突变KRAS的更高水平的IFN-γ和IL-17a，且KRAS特异性Th1和Th17反应增强，这种效应在末次接种后可持续3个月。重要的是，与对照组动物相比，免疫动物的肿瘤发生率显著降低。总之，黏膜接种KRAS疫苗的方法能诱导肺部产生局部KRAS特异性免疫反应，从而降低肿瘤发生率。

原文链接：

A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation