Abstract
Wilms tumor gene (WT1) possesses oncogenic functions and is expressed in various kinds of malignancies, which suggests that the genes 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 immunomonitoring, 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 of 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.
Keywords: WT1, peptide, CTL, helper, cancer, immunotherapy, vaccine
Anti-Cancer Agents in Medicinal Chemistry
Title: 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
Volume: 9 Issue: 7
Author(s): Yoshihiro Oka, Akihiro Tsuboi, Fumihiro Fujiki, Zheyu Li, Hiroko Nakajima, Naoki Hosen, Toshiaki Shirakata, Sumiyuki Nishida, Yusuke Oji, Ichiro Kawase and Haruo Sugiyama
Affiliation:
Keywords: WT1, peptide, CTL, helper, cancer, immunotherapy, vaccine
Abstract: Wilms tumor gene (WT1) possesses oncogenic functions and is expressed in various kinds of malignancies, which suggests that the genes 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 immunomonitoring, 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 of 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.
Export Options
About this article
Cite this article as:
Oka Yoshihiro, Tsuboi Akihiro, Fujiki Fumihiro, Li Zheyu, Nakajima Hiroko, Hosen Naoki, Shirakata Toshiaki, Nishida Sumiyuki, Oji Yusuke, Kawase Ichiro and Sugiyama Haruo, 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, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (7) . https://dx.doi.org/10.2174/187152009789056958
DOI https://dx.doi.org/10.2174/187152009789056958 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Role of Parthenolide in Intracellular Signalling Processes: Review of Current Knowledge
Current Signal Transduction Therapy Molecular Imaging of Therapeutic Potential of Reporter Probes
Current Drug Targets Effect of Number of Bifunctional Chelating Agents on the Pharmacokinetics and Immunoreactivity of 177Lu-labeled Rituximab: A Systemic Study
Anti-Cancer Agents in Medicinal Chemistry Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Recent Progress in the Development of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents Tetraspanins - Gateways for Infection
Infectious Disorders - Drug Targets Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy
Current Drug Targets Thiopurine S-Methyltransferase as a Pharmacogenetic Biomarker: Significance of Testing and Review of Major Methods
Cardiovascular & Hematological Agents in Medicinal Chemistry Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair
Current Pharmaceutical Design Glutaminase Isoenzymes as Key Regulators in Metabolic and Oxidative Stress Against Cancer
Current Molecular Medicine Control of Protein Synthesis in Malignant Transformation - the Role of eIF4E and the eIF4E Binding Proteins in the Regulation of Apoptosis
Current Cancer Therapy Reviews New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer
Current Pharmaceutical Design Structure and Ligand-based Design of P-glycoprotein Inhibitors: A Historical Perspective
Current Pharmaceutical Design Targeting DNA Minor Groove by Hybrid Molecules as Anticancer Agents
Current Medicinal Chemistry Common Pathways in Health Benefit Properties of RSV in Cardiovascular Diseases, Cancers and Degenerative Pathologies
Current Pharmaceutical Biotechnology Ocular Toxicities in Cancer Therapy: Still Overlooked
Current Cancer Therapy Reviews Cilostazol as a Unique Antithrombotic Agent
Current Pharmaceutical Design New Insights Into the Molecular Mechanisms of Action of Bisphosphonates
Current Pharmaceutical Design From Na+/K+-ATPase and Cardiac Glycosides to Cytotoxicity and Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Targeted α-Particle Therapy: A Clinical Overview
Current Radiopharmaceuticals