WT1: A Priority Tumor Antigen1
The Wilms’ tumor 1 (WT1) protein is expressed in various types of hematologic malignancies and solid tumors.2 WT1 has been shown to enable invasion and metastasis, and promote resistance to radiation and chemotherapy.3,4
WT1 as a Potential Therapeutic Target5
WT1 has multiple immunogenic epitopes and is capable of eliciting both cytotoxic and helper T–lymphocyte responses.5-7
WT1 was ranked 1st among 75 antigens that were evaluated by the National Cancer Institute to prioritize cancer antigens* for therapeutic targeting.1
Focusing on WT1 in GBM
WT1 is a known driver of glioblastoma (GBM) progression and is highly expressed in approximately 80% of GBM tumors.1,5,8 However, it is typically absent in normal brain tissue.8
Understanding the potential role of WT1 as an antigen in GBM could inform development of immunotherapy strategies.5
HLA=human leukocyte antigen; TCR=T-cell receptor.
*Criteria to prioritize cancer antigens: 1. therapeutic function, 2. immunogenicity, 3. role of the antigen in oncogenicity, 4. specificity, 5. expression level and percent of antigen-positive cells, 6. stem cell expression, 7. number of patients with antigen-positive cancers, 8. number of antigenic epitopes, 9. cellular location of antigen expression.1
- Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a National Cancer Institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17):5323-5337.
- Kijima N, Hashimoto N, Chiba Y, Fujimoto Y, Sugiyama H, Yoshimine T. Functional roles of Wilms’ tumor 1 (WT1) in malignant brain tumors. In: van den Heuvel-Eibrink M, ed. Wilms Tumor. Brisbane, Australia: Codon Publications; 2016:261-272.
- Qi XW, Zhang F, Wu H, et al. Wilms’ tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis. Sci Rep. 2015;5(8924).
- Chidambaram A, Fillmore HL, Van Meter TE, Dumur CI, Broaddus WC. Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness. J Neurosurg. 2012;116(4):843-853.
- Sugiyama H. WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol. 2010;40(5):377-387.
- Sugiyama H. Wilms’ tumor gene WT1: its oncogenic function and clinical application. Int J Hematol. 2001;73(2):177-187.
- Doubrovina E, Carpenter T, Pankov D, Selvakumar A, Hasan A, O’Reilly RJ. Mapping of novel peptides of WT-1 and presenting HLA alleles that induce epitope-specific HLA restricted T cells with cytotoxic activity against WT-1(+) leukemias. Blood. 2012;120(8):1633-1646.
- Chen MY, Clark AJ, Chan DC, et al. Wilms’ tumor 1 silencing decreases the viability and chemoresistance of glioblastoma cells in vitro: a potential role for IGF-1R de-repression. J Neurooncol. 2011;103(1):87-102.