Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilms' tumor gene WT1 is expressed in various kinds of cancers. Human WT1-specific cytotoxic T lymphocytes (CTLs) were generated, and mice immunized with WT1 peptide rejected challenges by WT1-expressing cancer cells without auto-aggression to normal organs. Furthermore, WT1 antibodies and WT1-specific CTLs were detected in cancer patients, indicating that WT1 protein was immunogenic. These findings provided us with the rationale for cancer immunotherapy targeting WT1. Clinical trials of WT1 peptide vaccination for cancer patients were started, and WT1 vaccination-related immunological responses and clinical responses, including reduction of leukemic cells, reduction of M-protein amount in myeloma, and shrinkage of solid cancer, were observed. Valuable information about immune responses against tumor antigens can be obtained by the analysis of samples from the vaccinated patients, which should lead to further improvement of cancer vaccine.
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PMID:WT1 peptide vaccine for the treatment of cancer. 1850 32

Cancer immunotherapy targeting tumor-associated antigens is now being developed. Wilms' tumor gene WT1-encoding protein is one of the promising target antigens for cancer immunotherapy, because the gene has an oncogenic function and is expressed in many kinds of malignancies. Furthermore, a series of investigations indicated that WT1 protein was highly immunogenic in cancer patients. Based on the analysis of anchor residues that were important for the interaction between peptides and HLA class I molecules, WT1 cytotoxic T lymphocyte (CTL) epitopes with the restriction of HLA-A 0201 and HLA-A 2402 were identified, and clinical trials of WT1 peptide vaccination for cancer patients with these HLA class I types were started. The vaccination-driven immunological and/or clinical responses were reported in patients with myeloid malignancies, multiple myeloma, and several solid cancers. Pediatric malignancies also may be target diseases for WT1 peptide vaccination in the future. Addition of HLA class II-restricted WT1 helper epitope peptide, chemotherapy, or molecular-target-based drug to WT1 CTL epitope peptide-based vaccination may enhance the power and usefulness of WT1 peptide vaccine. Other modalities, including gene therapy using genes encoding WT1-specific T cell receptor or DNA vaccination, are also expected to be developed.
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PMID:"Cancer antigen WT1 protein-derived peptide"-based treatment of cancer -toward the further development. 1907 52

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.
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PMID: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. 1953 72

Monitoring patients with multiple myeloma during and after treatment for the presence of residual myeloma cells (minimal residual disease - MRD) has been shown to give a major insight into the effectiveness of treatment. It has been reported that Wilms' tumor gene (WT1) expression levels measured by real-time quantitative polymerase chain reaction was useful as an indicator of minimal residual disease in leukemia and myelodysplastic syndrome. The aim of this study was to measure levels of WT1 expression, in order to find a possible association between the expression of this gene and multiple myeloma at diagnosis. If an association was found, the WT1 gene could be evaluated as an MRD marker by comparison with other prognostic factors. We investigated peripheral blood WT1 expression level measured by real-time light cycler quantitative polymerase chain reaction in 50 newly diagnosed multiple myeloma patients. The normal WT1 gene copy number was found to be <23/microl cDNA and all patients with myeloma were found to have normal WT1-mRNA levels. On this basis WT1 expression analyses is unlikely to be a useful genetic marker for routine clinical use in multiple myeloma patients at diagnosis.
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PMID:Expression of WT1 gene in multiple myeloma patients at diagnosis: is WT1 gene expression a useful marker in multiple myeloma? 2013 61

Despite high-dose chemotherapy followed by autologs stem-cell transplantation as well as novel therapeutic agents, multiple myeloma (MM) remains incurable. Following the general trend towards personalized therapy, targeted immunotherapy as a new approach in the therapy of MM has emerged. Better progression-free survival and overall survival after tandem autologs/allogeneic stem cell transplantation suggest a graft versus myeloma effect strongly supporting the usefulness of immunological therapies for MM patients. How to induce a powerful antimyeloma effect is the key issue in this field. Pivotal is the definition of appropriate tumor antigen targets and effective methods for expansion of T cells with clinical activity. Besides a comprehensive list of tumor antigens for T cell-based approaches, eight promising antigens, CS1, Dickkopf-1, HM1.24, Human telomerase reverse transcriptase, MAGE-A3, New York Esophageal-1, Receptor of hyaluronic acid mediated motility and Wilms' tumor gene 1, are described in detail to provide a background for potential clinical use. Results from both closed and on-going clinical trials are summarized in this review. On the basis of the preclinical and clinical data, we elaborate on three encouraging therapeutic options, vaccine-enhanced donor lymphocyte infusion, chimeric antigen receptors-transfected T cells as well as vaccines with multiple antigen peptides, to pave the way towards clinically significant immune responses against MM.
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PMID:T cell-based targeted immunotherapies for patients with multiple myeloma. 2519 87

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.
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PMID: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. 2904 Oct 12