Long-term maintenance of anti-tumor immune responses by vaccination with tri-WT1 peptide cancer vaccine WT1 Trio
Ontology highlight
ABSTRACT:
DISEASE(S): Thymic Cancer Thymoma Soft Tissue Sarcoma Malignant Glioma Salivary Gland Cancer Head And Neck Mucoepidermoid Carcinoma Olfactory Neuroblastoma Head And Neck Mucosal Malignant Melanoma Ophthalmic Malignant Melanoma Cancer Of The External Auditory Canal Testicular Cancer Cancer Of Penis Adrenal Cancer Malignant Mesothelioma Cancer Of The Small Intestine Merkel Cell Carcinoma Cutaneous Lymphoma (rare Cancers Listed Above)
PROVIDER: 2638831 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: A patient is vaccinated with Montanide ISA51-adjuvanted WT1 Trio cancer vaccine consisting of two WT1 CTL peptides (WT1-126 and WT1-235) and one WT1 HTL peptide (WT1-332) (2mg each) seven times at the interval of two weeks.
Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction and serum levels of WT1 peptide IgG autoantibody at 1M, 2M, and 3M of WT1 Trio vaccine.
Study Design: Single arm Non-randomized
| 2638832 | ecrin-mdr-crc
Project description:We report the the identification of chrosomal regions bound by the Wilms' tumor suppressor gene WT1 during embryonic mouse kidney development. Two indepednent ChIP-Seq experiments on microdissected E18.5 developing mouse kidneys were carried out using either WT1-specific or IgG-antibodies as a negative control.
2014-06-15 | E-GEOD-58179 | biostudies-arrayexpress
Project description:The activation of CD4+ T helper (Th) cells is crucial for the induction of cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into T-lineage cells (iPS-T cells). Although iPS-T cells retained the same T-cell receptor (TCR) as the original Th clone, their gene expression patterns resembled those of group 1 innate lymphoid cells, and CD4 molecule, an essential co-receptor in TCR-mediated Th responses, was not expressed. The transduction of CD4 genes into iPS-T cells enhanced b3a2 peptide–specific responses. iPS-T cells contained a subpopulation that up-regulates CD40 ligand (CD40L) in response to IL-2 and IL-15. Besides CD4 expression, CD40Lhigh iPS-T cells induced antigen-specific DC maturation characterized by enhanced CD83, CD86, and CCR7. In the presence of Wilms tumor 1 (WT1) peptide, DCs conditioned by CD4-modified CD40Lhigh iPS-T cells stimulated the priming of WT1-specific CTLs. These CTLs eliminated WT1 peptide-expressing CML cell lines in vitro and in vivo. Our findings indicate CD4 modification and purification of CD40Lhigh iPS-T cells generates T helper-like cells that induce effective anti-leukemic CTL responses via DC maturation and suggest feasibility of the cells for adoptive immunotherapy against leukemia.
2018-01-31 | GSE94332 | GEO
Project description:K-ras is one of the most frequently mutated human oncogenes. Activation of K-ras can lead to either senescence or proliferation in primary cells. The precise mechanism governing these distinct outcomes remains unclear. Here we utilized a loss-of-function screen to assess the role of specific genes identified as potential key regulators of K-ras driven oncogenesis. Using this approach, we identify the transcription factor Wt1 as an inhibitor of senescence in primary cells expressing oncogenic K-ras. Deletion or suppression of Wt1 expression leads to senescence of primary cells expressing oncogenic K-ras under the control of the native promotor at physiological levels, but has no effect on cells expressing wild-type K-ras. Wt1 contributes to K-ras driven lung tumorigenesis in vivo and loss of Wt1 is specifically deleterious to human lung cancer cell lines that are dependent on oncogenic K-ras. Taken together, these observations reveal a novel role for Wt1 as a key regulator of the complex genetic network required for the oncogenic effect of the small GTPase K-ras. We compare the expression profiles of Wild type, K-ras mutant, Wt1-null, and double K-ras mutant/Wt1-null mouse embryonic fibroblasts (MEFs). The study provides insights into the transcriptional role of Wt1 in the context of oncogenic K-ras.
2010-03-01 | GSE15325 | GEO
Project description:Gain-of-function mutations in exon 3 of beta-catenin (CTNNB1) are specific for Wilms' tumors that have lost WT1, but 50% of WT1-mutant cases lack such "hot spot" mutations. To ask whether stabilization of beta-catenin might be essential after WT1 loss, and to identify downstream target genes, we compared expression profiles in WT1-mutant versus WT1 wild-type Wilms' tumors. Supervised and nonsupervised hierarchical clustering of the expression data separated these two classes of Wilms' tumor. The WT1-mutant tumors overexpressed genes encoding myogenic and other transcription factors (MOX2, LBX1, SIM2), signaling molecules (TGFB2, FST, BMP2A), extracellular Wnt inhibitors (WIF1, SFRP4), and known beta-catenin/TCF targets (FST, CSPG2, CMYC). Beta-Catenin/TCF target genes were overexpressed in the WT1-mutant tumors even in the absence of CTNNB1 exon 3 mutations, and complete sequencing revealed gain-of-function mutations elsewhere in the CTNNB1 gene in some of these tumors, increasing the overall mutation frequency to 75%. Lastly, we identified and validated a novel direct beta-catenin target gene, GAD1, among the WT1-mutant signature genes. These data highlight two molecular classes of Wilms' tumor, and indicate strong selection for stabilization of beta-catenin in the WT1-mutant class. Beta-Catenin stabilization can initiate tumorigenesis in other systems, and this mechanism is likely critical in tumor formation after loss of WT1. Experiment Overall Design: Identification of WNT/Beta-Catenin or WT1 target genes. 39 individual samples.
2008-06-14 | E-GEOD-6120 | biostudies-arrayexpress
Project description:K-ras is one of the most frequently mutated human oncogenes. Activation of K-ras can lead to either senescence or proliferation in primary cells. The precise mechanism governing these distinct outcomes remains unclear. Here we utilized a loss-of-function screen to assess the role of specific genes identified as potential key regulators of K-ras driven oncogenesis. Using this approach, we identify the transcription factor Wt1 as an inhibitor of senescence in primary cells expressing oncogenic K-ras. Deletion or suppression of Wt1 expression leads to senescence of primary cells expressing oncogenic K-ras under the control of the native promotor at physiological levels, but has no effect on cells expressing wild-type K-ras. Wt1 contributes to K-ras driven lung tumorigenesis in vivo and loss of Wt1 is specifically deleterious to human lung cancer cell lines that are dependent on oncogenic K-ras. Taken together, these observations reveal a novel role for Wt1 as a key regulator of the complex genetic network required for the oncogenic effect of the small GTPase K-ras. We compare the expression profiles of Wild type, K-ras mutant, Wt1-null, and double K-ras mutant/Wt1-null mouse embryonic fibroblasts (MEFs). The study provides insights into the transcriptional role of Wt1 in the context of oncogenic K-ras. MEFs were infected with adenoviral Cre to activate K-ras (6 samples), knockout Wt1 (5 samples), both activate K-ras and knockout Wt1 (7 samples). As a control, MEFs were infected with adenoviral GFP (5 samples). RNA was isolated using Trizol 7 days after infection. RNA was further prepared by passage over an RNeasy column. cDNA synthesis, biotinylation of cRNA and hybridization to mouse Genechip 430A v2 containing 39,000 probes was performed according to the manufacturer's instructions (Affymetrix, Santa Clara). Microarray data was normalized with Expression Console software (Affymetrix, Santa Clara) using RMA algorithms.
2010-03-06 | E-GEOD-15325 | biostudies-arrayexpress
Project description:K-ras is one of the most frequently mutated human oncogenes. However, activation of K-ras can lead to either senescence or proliferation in primary cells. The precise mechanism governing these distinct outcomes remains unclear. Here we describe a novel loss-of-function screen to assess the role of specific genes identified as potential key regulators of K-ras driven oncogenesis. Using this approach, we identify the transcription factor Wt1 as an inhibitor of senescence in primary cells expressing oncogenic K-ras. Deletion or suppression of Wt1 expression leads to senescence of primary cells expressing oncogenic K-ras under the control of the native promotor and at physiological levels, but had no effect on cells expressing wild-type K-ras. Furthermore, loss of Wt1 in lung cancer cell lines that harbor mutant K-ras leads to apoptosis. Taken together, these observations reveal a novel role for Wt1 as a key regulator of the complex genetic network required for the oncogenic effect of the small GTPase K-ras. We compare the expression profiles of K-ras mutant mouse cell line (LKR13) upon shRNA knockdown of K-ras itself or Wt1. The study provides insights into the transcriptional role of Wt1 in the context of oncogenic K-ras.
2010-03-01 | GSE15326 | GEO
Project description:The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism (SNP) array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed a notorious absence of acquired chromosomal changes at relapse. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2/9 samples. Subsequent analysis showed WT1 mutations in 28/211 (13.2%) of pediatric and 10/85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frameshift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3 and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall these results show that overt chromosomal instability does not seem to be a major mutagenic mechanism contributing to disease progression in T-ALL and the presence of WT1 mutations as a recurrent genetic alteration in T-ALL.
2009-08-10 | GSE15931 | GEO
Project description:N-degradomic analysis of proteolytic processing in WT1 heterozygous mice, suffering from genetically induced chronic kidney injury, compared to wild type
2021-02-15 | PXD023292 | Pride
Project description:K-ras is one of the most frequently mutated human oncogenes. However, activation of K-ras can lead to either senescence or proliferation in primary cells. The precise mechanism governing these distinct outcomes remains unclear. Here we describe a novel loss-of-function screen to assess the role of specific genes identified as potential key regulators of K-ras driven oncogenesis. Using this approach, we identify the transcription factor Wt1 as an inhibitor of senescence in primary cells expressing oncogenic K-ras. Deletion or suppression of Wt1 expression leads to senescence of primary cells expressing oncogenic K-ras under the control of the native promotor and at physiological levels, but had no effect on cells expressing wild-type K-ras. Furthermore, loss of Wt1 in lung cancer cell lines that harbor mutant K-ras leads to apoptosis. Taken together, these observations reveal a novel role for Wt1 as a key regulator of the complex genetic network required for the oncogenic effect of the small GTPase K-ras. We compare the expression profiles of K-ras mutant mouse cell line (LKR13) upon shRNA knockdown of K-ras itself or Wt1. The study provides insights into the transcriptional role of Wt1 in the context of oncogenic K-ras. LKR13 cells were infected with plko.1s vectors carrying one of two shRNAs against K-ras or Wt1. Control cells were infected with an shRNA against GFP. 48 hours after infection, cells were selected with puromycin for 3 days. RNA was isolated using Trizol 7 days after infection. RNA was further prepared by passage over an RNeasy column. cDNA synthesis, biotinylation of cRNA and hybridization to mouse Genechip 430A v2 containing 39,000 probes was performed according to the manufacturerâ??s instructions (Affymetrix, Santa Clara). Microarray data was normalized with Expression Console software (Affymetrix, Santa Clara), using RMA algorithms.
2010-03-07 | E-GEOD-15326 | biostudies-arrayexpress