T cell receptor recognizing HLA-A2–peptide complexes derived from EO2401 (EO2401-specific TCR)

The T cell receptor (TCR) recognizing HLA-A2–peptide complexes derived from EO2401 is a specialized immune receptor that mediates the recognition of microbiome-derived OncoMimic peptides (Enterome, 2024). These peptides, which comprise the EO2401 vaccine, are designed to mimic specific tumor-associated antigens (TAAs) such as IL13Ra2, Survivin (BIRC5), and FOXM1, which are frequently overexpressed in various malignancies (Migliorini et al., 2021). When these mimic peptides are presented by the HLA-A*02:01 molecule on antigen-presenting cells, they bind to the TCR, triggering the activation and clonal expansion of CD8+ cytotoxic T cells (ClinicalTrials.gov, NCT04116658). These activated T cells then cross-react with the actual human TAAs presented on the surface of tumor cells, leading to targeted cell lysis (Reardon et al., 2022). This target is currently being evaluated in clinical trials for patients with glioblastoma and adrenal tumors who are HLA-A2 positive. The therapeutic goal is to leverage the pre-existing memory T cell repertoire against commensal bacteria to mount a potent anti-tumor response. Safety considerations primarily involve ensuring that the TCR-mediated response does not cause significant damage to healthy tissues expressing low levels of the targeted TAAs.

Other names

EO2401-specific T-cell receptorHLA-A*02:01-restricted EO2401 TCROncoMimic-specific TCRMicrobiome-derived peptide-specific TCR

Induction of T cell activation and proliferation via TCR binding to microbiome-derived mimic peptides presented on HLA-A2, facilitating cross-reactive immune attack against tumor-associated antigens (Enterome, 2024).