WT1 (Wilms Tumor-1 protein)

Class

Multivalent heteroclitic peptide cancer vaccine

Pathway

WT1-directed anti-tumor immune activation

WT1, the Wilms Tumor-1 protein, is a zinc finger transcription factor that normally helps regulate cell growth and organ development, particularly in the kidneys and blood-forming tissue. In healthy adult tissue its expression is very limited, but many cancers, including several leukemias and solid tumors, express it at high levels, where it appears to support survival and proliferation of malignant cells. Because it is expressed inside the cell rather than on the surface, WT1 cannot be targeted directly with antibodies; instead, small fragments of the protein are naturally displayed on the cell surface by MHC molecules, marking WT1-high cells for recognition by the immune system. A multivalent heteroclitic peptide vaccine exploits this by presenting several modified WT1 peptide fragments designed to bind MHC more strongly and provoke a more vigorous immune response than the natural sequence would. Using multiple peptides, rather than one, aims to engage several types of immune cells and reduce the chance that tumor cells escape by losing a single target epitope. This approach is being explored broadly in cancers where WT1 overexpression is common, with the underlying rationale of training the immune system to recognize and eliminate WT1-expressing malignant cells while sparing normal tissue.