FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• FOXM1 is a transcription factor highly expressed in many cancers, driving tumor progression.
• Targeting cancer-specific antigens with immunotherapy is a promising approach.

Purpose of the Study:

• To evaluate the immunogenicity of FOXM1.
• To investigate the feasibility of targeting FOXM1 using T cell receptor (TCR) engineering for cancer therapy.

Main Methods:

• Identification of FOXM1-derived epitopes presented on HLA-A*02:01, HLA-A*24:02, and HLA-A*23:01.
• Generation and validation of TCR-engineered T cells (TCR-T cells) for specificity and sensitivity.
• Assessment of anti-tumor efficacy via adoptive transfer of TCR-T cells in a murine tumor model.

Main Results:

• FOXM1-derived epitopes were identified as immunogenic, triggering T cell activation and cytotoxic responses.
• TCR-T cells demonstrated specificity and sensitivity against FOXM1 epitopes.
• Adoptive transfer of TCR-T cells significantly reduced tumor growth and prolonged survival in vivo.

Conclusions:

• FOXM1 is immunogenic and represents a viable target for TCR-based immunotherapy.
• TCR engineering targeting FOXM1 shows significant anti-tumor potential in preclinical settings.