WT1 peptide vaccine as a paradigm for "cancer antigen-derived peptide"-based immunotherapy for malignancies: successful induction of anti-cancer effect by vaccination with a single kind of WT1 peptide.

Abstract

Wilms' tumor gene (WT1) possesses oncogenic functions and is expressed in various kinds of malignancies, which suggests that the gene's product, the WT1 protein, should be one of the most promising cancer antigens. In fact, the WT1 protein was shown to be highly immunogenic in cancer patients. WT1 peptides that could induce WT1-specific CTLs (WT1 CTL peptides) were identified, and vaccination of cancer patients with these WT1 CTL peptides induced immunological responses, which were assessed by ex vivo immuno-monitoring, such as the tetramer assay, and in vivo immuno-monitoring, such as the peptide-specific delayed type hypersensitivity reaction. The induced immunological responses then led to clinical responses such as solid tumor shrinkage, a decrease in leukemia cells, and reduction of M-protein (multiple myeloma). Long-term stabilization of disease with good quality of life, which might be characteristic of cancer vaccine therapy, was also reported. It is noteworthy that injection with a "single" kind of WT1 peptide elicited an immunological response strong enough to induce a clinical response, indicating that the WT1 peptide vaccine has therapeutic potential. The number of reports of the successful treatment of cancer patients (not only adult but also childhood malignancies) with WT1 vaccination is increasing. Strategies for further improvement in the efficacy of therapy, including combined use of chemotherapy drugs, molecular-target-based drugs, or WT1 helper peptides, are being proposed. WT1 peptide vaccination in an "adjuvant setting" should be considered a promising treatment to protect against progression or relapse of malignancies in cases with minimal residual disease.

• Authors: Yoshihiro Oka, Akihiro Tsuboi, Fumihiro Fujiki, Zheyu Li, Hiroko Nakajima, Naoki Hosen, Toshiaki Shirakata, Sumiyuki Nishida, Yusuke Oji, Ichiro Kawase, Haruo Sugiyama
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 9 Issue 7 Pg. 787-97 (Sep 2009) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 19538172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Peptides
• WT1 Proteins

Topics

• Amino Acid Sequence
• Animals
• Antigens, Neoplasm (immunology)
• Cancer Vaccines (administration & dosage, immunology, therapeutic use)
• Clinical Trials as Topic
• Disease Models, Animal
• Humans
• Immunotherapy
• Mice
• Neoplasms (immunology, therapy)
• Peptides (administration & dosage, chemistry, immunology, therapeutic use)
• T-Lymphocytes, Cytotoxic (immunology)
• WT1 Proteins (chemistry)