DARKFOX-A3 peptide-HLA-A*03:01 complex (DARKFOX-A3 pHLA)

The DARKFOX-A3 peptide-HLA-A*03:01 complex is a tumor-specific antigen complex consisting of a peptide derived from an alternative open reading frame (altORF) of the FOXM1 gene, presented by the HLA-A*03:01 allele [2, 3]. Discovered by Enara Bio using their EDAPT platform, this “Dark Antigen” is highly prevalent across multiple solid tumors, including esophageal, lung, breast, and colorectal cancers, while maintaining minimal expression in normal tissues [3, 5]. The complex serves as a target for T-cell redirection therapies, most notably the bispecific T-cell engager ENA101, which utilizes a high-affinity T-cell receptor (TCR) mimic to bind the peptide-HLA interface [4, 6]. By facilitating the formation of an immunological synapse between cytotoxic T cells and tumor cells, the complex enables potent and selective tumor cell lysis [5, 7]. Its discovery highlights the potential of the “dark proteome” to provide novel, shared targets for immunotherapy in patients with common HLA genotypes [6, 10].

Other names

DARKFOX-A3DARKFOX peptide-HLA-A*03:01 complexFOXM1 altORF peptide-HLA complexDark Antigen-A3

T-cell redirection and activation via bispecific T-cell engager (TCE) binding to the peptide-HLA complex and CD3 on T cells.