1140 Labyrinthin as a potential neoantigen for oncogene-driven and non-oncogene-driven lung adenocarcinomas

BackgroundImmune checkpoint inhibitors (ICIs) have inferior clinical response in patients with oncogene-driven lung adenocarcinoma (LUAD). There is also an unmet need for patients with non-oncogene-driven LUAD who failed first line ICI-containing treatment. Labyrinthin (LAB) is a novel cancer neoantigen expressed on the surface of adenocarcinoma cells of various cancer types including LUAD. We recently showed that LAB was expressed in LUAD by immunohistochemistry and is an independent prognostic factor for LUAD. The objective of this study was to determine if LAB is a target in different LUAD subgroups.MethodsLAB mRNA expression was assessed in The Cancer Genome Atlas (TCGA) LUAD dataset. LAB-specific mRNA expression was determined by averaging expression of exons specific to LAB and not the related splice variant aspartyl/asparaginyl beta-hydroxylase (ASPH). Patients with tyrosine-kinase inhibitor (TKI)-sensitive driver oncogenes were defined as those with an FDA-approved targeted therapy (e.g., mutations in EGFR, BRAF V600E, MET E14SP, ERBB2 and gene fusions in ALK, ROS1 and RET). Patients with other oncogenes included other BRAF mutations, KRAS, HRAS, NRAS and MAP2K).The results are validated in an independent cohort of clinically annotated patients with LUAD.ResultsAs expected, TKI-sensitive oncogene-driven LUAD (n=54) had statistically lower tumor mutational burden (TMB) (2.8 mut/MB, p