Emily Bontekoe, M. Zhang, Peixin Jiang, Amanda Montoya, Yulia V. Shulga, Jared K. Slone, Emily Paul, Christopher Polera, Sarah Forward, Barbara Nassif Rausseo, Emane Rose Assita, Changsheng Xing, David Molkentine, Benjamin B. Morris, Isabella Polic, J. Roszik, Ricardo Salgado, Aria Vaishnavi, Drew C. Deniger, Hai T. Tran, Don L. Gibbons, Ara A. Vaporciyan, Maura L. Gillison, Ignacio I. Wistuba, Lydia E. Kavraki, Jianjun Zhang, Gregory Lizée, C. Yee, Patrick Hwu, Sheldon J. J. Kwok, Alex M. Jaeger, John V. Heymach, Alexandre Reuben
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 a significant reduction in tumor growth, as well as significantly prolonged survival in a tumor-bearing immunocompromised murine model. Our studies confirm the immunogenicity of FOXM1 and feasibility of targeting this antigen using TCR engineering.