Abstract
Lung adenocarcinoma (LUAD) is classified as Non-Small-Cell Lung Cancer (NSCLC), one of the most malignantcancers due to its poor prognosis and fast progression. Its resistance to chemotherapy, immunosuppressive tumormicroenvironment (TME), and frequent immune evasion also impose enormous obstacles in treating LUAD. However,previous research found that these tumor cells resistant to chemotherapies commonly increase their production ofintracellular reactive oxygen species (ROS) due to high mitochondria activity. Antioxidants like glutathione (GSH)are also highly produced to maintain their redox homeostasis. Therefore, the depletion of antioxidants which can leadto intratumoral accumulation of ROS to cytotoxic levels, provides a new therapeutic target. Besides, the high levelof extracellular ROS also significantly contributes to the immunosuppressive characteristic of TME, which exhaustsactivated T cells. This work provides the framework for a novel combinational therapy based on a multiple-neoantigenvaccine to avoid immune evasion. Two types of nanoparticles further boost the vaccine’s efficacy against tumors, onedepleting intratumoral GSH and scavenging extracellular ROS. Anticipated results are shown from various aspects,hoping the innovative treatment can effectively improve the survival rate with few side effects.
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