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.

KRAS 突变通常发生在肺部，可导致非小细胞肺癌 (NSCLC) 的发展。虽然突变的 KRAS 蛋白是一种新抗原，但它通常不会在粘膜/上皮表面产生有效的抗肿瘤免疫反应。尽管如此，突变的 KRAS 仍然是免疫治疗的潜在靶点，因为在动物模型中针对这种蛋白质的免疫靶向可以有效消除肿瘤细胞。我们尝试使用突变型和野生型 KRAS 肽与纳米乳 (NE) 佐剂相结合来开发 KRAS 疫苗。该方法的功效在诱导突变型 KRAS 小鼠肺肿瘤模型中进行了测试。使用 NE 和 KRAS 肽对动物进行鼻内免疫。这些动物的淋巴结和脾脏中CD4 ⁺ FoxP3 ⁺ T 细胞均减少。^{免疫动物还对 CD8 +} T 细胞产生的突变 KRAS 显示出更高的 IFN-γ 和 IL-17a 水平，并且 KRAS 特异性 Th1 和 Th17 反应增强，并在最后一次疫苗接种后持续 3 个月。重要的是，与对照动物相比，免疫动物的肿瘤发病率显着降低。总之，粘膜 KRAS 疫苗接种方法证明能够在肺部诱导局部 KRAS 特异性免疫反应，从而降低肿瘤发病率。