Combined ROS-related therapy improves the efficacy of multipleneoantigen vaccines against LUAD

Abstract

Lung adenocarcinoma (LUAD) is classified as Non-Small-Cell Lung Cancer (NSCLC), one of the most malignant
cancers due to its poor prognosis and fast progression. Its resistance to chemotherapy, immunosuppressive tumor
microenvironment (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 of
intracellular 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 lead
to intratumoral accumulation of ROS to cytotoxic levels, provides a new therapeutic target. Besides, the high level
of extracellular ROS also significantly contributes to the immunosuppressive characteristic of TME, which exhausts
activated T cells. This work provides the framework for a novel combinational therapy based on a multiple-neoantigen
vaccine to avoid immune evasion. Two types of nanoparticles further boost the vaccine’s efficacy against tumors, one
depleting 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.