Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy.

Abstract

The identification of human Wilms' tumor gene 1 (WT1) protein-derived cytotoxic T lymphocyte (CTL) epitopes and the in vivo efficacy of WT1 peptide-based immunotherapy in a mouse model were reported in 2000. This successful basic research led to clinical studies of a WT1 peptide vaccine, and a positive impact on clinical response was first demonstrated in 2003 in the form of a reduction in blast cells of vaccine-treated patients with myelodysplastic syndromes (MDS). Since then, data on WT1 peptide vaccine-treated patients with immunological and/or clinical response have been accumulated. MDS and acute myeloid leukemia were the major target diseases to provide proof of concept for the therapeutic potential of the WT1 peptide vaccine. WT1 vaccination-induced clinical responses or usefulness were also shown for chronic myeloid leukemia, multiple myeloma, and acute lymphoblastic leukemia, as well as various types of solid cancers. Non-Hodgkin's lymphoma and myeloproliferative neoplasms may also be target diseases because of their WT1 expression. Of note, recent clinical studies have demonstrated that patients with hematological malignancies who have minimal residual disease after chemotherapy or allogeneic hematopoietic stem cell transplantation may be cured by WT1 peptide vaccination. Further enhancement of the efficacy and usefulness of the WT1 peptide vaccine is expected.

• Authors: Yoshihiro Oka, Akihiro Tsuboi, Jun Nakata, Sumiyuki Nishida, Naoki Hosen, Atsushi Kumanogoh, Yusuke Oji, Haruo Sugiyama
• Journal: Oncology research and treatment (Oncol Res Treat) Vol. 40 Issue 11 Pg. 682-690 ( 2017) ISSN: 2296-5262 [Electronic] Switzerland
• PMID: 29041012 (Publication Type: Journal Article, Review)
• Copyright: © 2017 S. Karger GmbH, Freiburg.

Chemical References

• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Vaccines, Subunit
• WT1 Proteins
• WT1 protein, human

Topics

• Animals
• Cancer Vaccines (administration & dosage, immunology)
• Clinical Studies as Topic
• Epitopes, T-Lymphocyte (immunology)
• Hematologic Neoplasms (genetics, immunology, therapy)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (immunology, therapy)
• Mice
• Multiple Myeloma (immunology, therapy)
• Myelodysplastic Syndromes (immunology, therapy)
• Neoplasm, Residual (immunology, therapy)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (immunology, therapy)
• Treatment Outcome
• Vaccines, Subunit (administration & dosage, immunology)
• WT1 Proteins (genetics)