Wilms' tumor 1 peptide–Major Histocompatibility Complex (WT1-MHC)

The Wilms' tumor 1 (WT1) peptide–Major Histocompatibility Complex (MHC) is a tumor-associated antigen complex presented on the surface of various hematological and solid malignancies. WT1 is a zinc-finger transcription factor that plays a pivotal role in cell growth and differentiation; while it is highly expressed during embryogenesis, its expression in healthy adults is restricted to low levels in specific tissues like hematopoietic stem cells and renal podocytes (Cheever et al., 2009) [1]. In cancer cells, overexpressed WT1 is processed into peptides and presented by MHC Class I molecules, primarily HLA-A*02:01, making the intracellular protein visible to the immune system (Oka et al., 2004) [2]. This complex serves as a specific docking site for T-cell receptors (TCRs) and TCR-like therapeutic agents, enabling the selective destruction of tumor cells (Dao et al., 2013) [3]. Current therapeutic approaches include peptide vaccines designed to expand endogenous WT1-specific T cells, adoptive transfer of TCR-engineered T cells (TCR-T), and bispecific T-cell engagers. Targeting the WT1-MHC complex is particularly advantageous as it allows for the therapeutic targeting of a potent intracellular oncogene that cannot be reached by traditional monoclonal antibodies.

Other names

WT1-HLA complexHLA-A*02:01/WT1(126-134)HLA-A*02:01/WT1(235-243)Wilms tumor protein peptide-MHCWT1 pMHC

T-cell receptor (TCR) binding and activation leading to T-cell mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC).