HLA-A*02:01-Wilms' tumor 1 peptide complex (HLA-A*02:01/WT1)

The HLA-A*02:01-Wilms' tumor 1 (WT1) peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical neoantigen target in oncology [1]. WT1 is a transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), and several solid tumors, while maintaining low expression in normal adult tissues [2]. The HLA-A*02:01 allele presents specific WT1-derived epitopes, most notably the RMFPNAPYL (WT1 126-134) peptide, on the cell surface for recognition by the immune system [3]. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, TCR-like monoclonal antibodies, and peptide vaccines designed to elicit a robust cytotoxic T-lymphocyte response against WT1-positive cancer cells [4]. Because WT1 is an intracellular protein, the pMHC complex is the primary mechanism for the immune system to identify and eliminate cells expressing this oncogene [5]. Clinical development focuses on ensuring high specificity to avoid cross-reactivity with similar self-peptides and managing potential on-target effects in tissues like the kidney or bone marrow [6]. [1] Cheever et al. (2009) Clin Cancer Res; [2] Sugiyama (2010) Jpn J Clin Oncol; [3] Oka et al. (2004) Immunogenetics; [4] Dao et al. (2013) Sci Transl Med; [5] Van Driessche et al. (2003) Leukemia; [6] Lichtenegger et al. (2017) Leukemia.

Other names

WT1-A2HLA-A*02:01/WT1(126-134)RMFPNAPYL-HLA-A*02:01Wilms' tumor 1-derived peptide-HLA-A*02:01 complexHLA-A*0201/WT1

Recognition by T-cell receptors (TCRs) or TCR-like antibodies leading to targeted lysis of WT1-expressing cells.