Immunopeptidomics guided identification of neoantigens in non-small cell lung cancer

ABSTRACT: Discovery of tumour specific peptides (neoantigens) generating target specific personalised T cell therapies is difficult because of the complex relationship between genetic mutations and neoantigen presentation. Studies predicting neoantigens have a 5% success rate, and direct observations of neoantigens are even rarer. We have developed a mass spectrometry proteomics guided approach to identify neoantigens in non-small cell lung cancer (NSCLC). We hypothesised that by characterising the observable peptides presented by HLA molecules (the immunopeptidome) we might better predict which mutations lead to neoantigens. From a cohort of 24 NSCLC patients, we performed a detailed analysis of 3 adenocarcinoma and 3 squamous cell carcinoma samples. Our workflow identified neoantigens generating functional T cell responses in 5 out of 6 patients, with one directly observed neoantigen, and an overall response rate of 20% of predicted neoantigens.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

DISEASE(S): Lung Cancer

SUBMITTER: Alistair Bailey  

LAB HEAD: Paul J Skipp

PROVIDER: PXD028990 | Pride | 2026-07-03

REPOSITORIES: Pride