Identification of FOXM1 Epitopes in Lung Cancer

FOXM1 is highly expressed in various cancer types and considered a key driver of cancer progression. Accordingly, we evaluated the immunogenicity of FOXM1 and investigated the feasibility of targeting this transcription factor using T cell receptor (TCR) engineering. We identified epitopes derived from FOXM1 which were immunogenic on HLA-A*02:01, HLA-A*24:02, and HLA-A*23:01, endogenously-processed and presented, and resulted in T cell activation and cytotoxic T cell responses. Following the generation of TCR-T cells, sensitivity and specificity were confirmed by peptide dose-response and X-scan, respectively. Most importantly, adoptive transfer of TCR engineered T cells led to reduced tumor growth and prolonged survival in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) strain murine models bearing FOXM1 expressing subcutaneous tumors. Our studies confirm the immunogenicity of FOXM1 and feasibility of targeting this tumor-associated antigen using TCR-engineering.