WT1

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

Boston Biomedical, Inc. is a leading developer of next-generation cancer therapeutics designed to inhibit cancer stemness pathways and modify immune responses.

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

References

  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.
  2. 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.
  3. 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).
  4. 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.
  5. Sugiyama H. WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol. 2010;40(5):377-387.
  6. Sugiyama H. Wilms’ tumor gene WT1: its oncogenic function and clinical application. Int J Hematol. 2001;73(2):177-187.
  7. 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.
  8. 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.