WT1 cancer vaccine for the treatment and prevention

Abstract

Wilms’ tumor gene 1 (WT1) overexpresses in almost all kinds of hematological malignancies and solid tumors (hereinafter referred to as cancer). Therefore, WT1 protein is a ubiquitous tumor-associated antigen (TAA). Many clinical studies of WT1-targeted cancer immunotherapies (hereinafter referred to as WT1 cancer vaccine), including WT1 peptide vaccine, WT1 peptide-pulsed dendritic cell (WT1-DC) vaccine, and WT1 mRNA-electroporated dendritic cell (WT1 mRNA-DC) vaccine had been conducted for the treatment of almost all kinds of cancer. The clinical effect was promising, whereas the major side effects were the temporary fever and skin reaction on the vaccine injection sites and not significant. The appropriate combination therapy of WT1 cancer vaccine and chemotherapy enhanced WT1 immune response against cancer. Gemcitabine (GEM), for example, increased WT1 immune response through the promotion of the expression of WT1 antigen protein and HLA class I/II molecules in cancer. Furthermore, WT1 cancer vaccine immediately after hematopoietic stem cell transplantation (HSCT) induced sufficient WT1 immune response regardless of severe immunocompromised conditions and exerted sufficient clinical effect, suggesting that the immune condition immediately after HSCT should be suitable for the priming of WT1 immune response. Moreover, the combination therapy of WT1 cancer vaccine and immune checkpoint inhibitors (ICIs) was promising. Compared to the other TAAs, WT1 is especially unique in that it expresses not only in cancer cells but also in their stem cells at the quiescent state of cell-cycle, which are resistant to chemo-and radio-therapies. This uniqueness of WT1 largely contributes to cure cancer through the complete eradication of WT1-expressing cancer stem cells by WT1 immune response against them. Since the complete eradication of cancer stem cells is essential to cure cancer, and since only immune cells against cancer are considered to be able to kill the cancer stem cells at the quiescent state of cell-cycle, the introduction of immunotherapy, especially of WT1 cancer vaccine with sufficient safety is essential in the cure-oriented treatments of cancer. Accumulated clinical results suggest that WT1 cancer vaccine should be useful for cancer prevention, and the development of WT1 cancer prevention vaccine is awaited.