Wilms tumor protein 1 (WT1) (WT1)

Wilms tumor protein 1 (WT1) is a zinc-finger transcription factor that plays a dual role in human biology, acting as a critical regulator of organogenesis during embryonic development and as a potent oncogene in various adult malignancies [NIH, Wikipedia]. Although it was first identified as a tumor suppressor gene associated with pediatric Wilms tumor, its overexpression in a wide range of cancers, including acute myeloid leukemia (AML), mesothelioma, and ovarian cancer, has made it a high-priority target for cancer immunotherapy [PubMed, NIH]. WT1 is ranked as one of the top tumor-associated antigens (TAAs) due to its high immunogenicity and differential expression between malignant cells and normal tissues [NIH, AACR]. Therapeutic interventions primarily focus on active immunotherapy, such as peptide-based and dendritic cell vaccines (e.g., Galinpepimut-S), as well as adoptive T-cell therapies using TCR-engineered T cells [Wikipedia, NIH]. These treatments aim to induce a robust CD8+ and CD4+ T-cell response to eradicate WT1-expressing tumor cells and cancer stem cells, particularly in the setting of minimal residual disease to prevent relapse [PubMed, NIH]. Clinical trials have demonstrated that WT1-targeted therapies are generally well-tolerated, though monitoring for potential renal effects is necessary due to WT1 expression in podocytes [PubMed, NIH]. The development of these vaccines represents a significant advancement in precision oncology, offering a potential universal approach to treating WT1-positive malignancies [NIH, AACR].

Other names

WT1Wilms tumor 1Wilms tumor suppressorWT33AEWS-GUDNPHS4WAGRWIT-2

Induction of an active immune response through the presentation of WT1-derived peptides on HLA molecules, leading to the activation and expansion of WT1-specific CD8+ cytotoxic T lymphocytes and CD4+ helper T cells that target and lyse WT1-overexpressing malignant cells.