Wilms' tumor gene 1 immunotherapy in pelvic gynecological malignancies

Abstract

Pelvic gynecological malignancies account for 6% of all cancers. In the relapsed state, classical treatments are limited. There is an urgent need for new and personalized treatment. Wilms' tumor gene 1 (WT1) is the most important tumor-associated antigen. Although highly present in gynecological tumors, active immunotherapy against it is still underexplored. This review gives an insight into the importance of WT1 in pelvic gynecological malignancies and the first taken steps into the world of WT1 immunotherapy.

Keywords::

• DC
• dendritic cell
• immunotherapy
• ovarian cancer
• uterine cancer
• Wilms' tumor gene 1
• WT1

Financial & competing interests disclosure

A Coosemans has a postdoctoral mandate from the FWO (Fondsvoor Weteschappelijk Onderzoek Vlaanderen). SW Van Gool is Senior Clinical Investigator of the FWO. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pelvic gynecological account for 6% of all cancer.

• New therapeutic options are urgently needed in relapsed cancer cases.

• Wilms' tumor gene 1 (WT1) is the most important tumor-associated antigen (TAA). It is overexpressed in the tumor cells of the most frequent subtype of ovarian cancer and the most aggressive type of uterine cancer and in tumor cells and intratumoral blood vessels of the most common subtype of uterine cancer. For both uterine and ovarian cancer, WT1 most likely has a role in the malignant phenotype.

• Active immunotherapy relies on anticancer vaccines that are able to elicit an immune response against TAA in the human body. This can be performed in three ways: DNA vaccination, injection of TAA peptide/protein or dendritic cell (DC) immunotherapy, in which case the TAA is loaded on a carrier, the DC. Using a carrier offers a superior platform for stimulating TAA-specific immune responses in vivo.

• So far, a total of 59 patients have been treated with WT1 immunotherapy worldwide, or with WT1 peptide injection or with DC loaded with WT1 mRNA. No major oncological effects were seen. The reason is probably multifactorial: patients included in advanced stages with large tumor burden, the use of only one TAA, presentation of WT1 only in the context of MHC I and no effect on the immunosuppressive environment.

• Nevertheless, discrete oncological changes and immunological response could already be measured. DC immunotherapy holds much promise for pelvic gynecological malignancies, but the therapy needs to be ameliorated, both by increasing the immunogenicity of the vaccine and by influencing the tumor microenvironment.