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Updated: Mar 21, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer
Emily Bontekoe1, Minying Zhang1, Peixin Jiang1
1Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract:
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.
Insights
This study shows that the FOXM1 protein is immunogenic and can be targeted in cancer. T cell receptor (TCR) engineered T cells targeting FOXM1 effectively reduced tumor growth and improved survival in preclinical models.
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.
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