6048 results for "canc*"

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• Effector CD4 T Cells Convert Transient Responses to KRAS-Targeted Therapy into Long-Term Durable Remissions in Pancreatic Cancer

  Pancreatic ductal adenocarcinoma (PDAC) is refractory to most therapies, including immunotherapies in which reinvigoration of CD8 T cells is insufficient to induce durable long-term remissions. Direct KRAS inhibitors are clinically promising; however, acquired resistance is common. Using AI-assisted computational design, we developed a de novo IL-21 mimic, 21h10, with enhanced stability and high signaling potency in both humans and mice. Using an orthotopic PDAC mouse model, we evaluated responses and relapse following KRAS inhibitor treatment and demonstrated that, unlike combinations with chemotherapy or checkpoint blockade, the combination of 21h10 and KRAS inhibition is curative. Single-cell transcriptional profiling with TCR-seq revealed oligoclonal expansion of effector Th1-polarized CD4 T cells and depletion of Tregs. To evaluate the efficacy of 21h10 in human samples, we performed single-cell RNA-seq analyses on treatment-naive specimens following short-term ex vivo treatment with 21h10. This dataset consists of Illumina NovaSeq sequencing output (FASTQ files) generated from tumor libraries prepared using the 10x Genomics Single Cell 5′ Immune Profiling platform. FASTQ files are provided for gene expression (GEX), TCR, and, for multiplexed samples, HTO libraries.

  Study phs004509

• NCTN_NCORP: Phase III Trial of LHRH Analog Administration During Chemotherapy to Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer (S0230)

  Study ID: S0230NCT Number: NCT00068601 SWOG Cancer Research NetworkSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN_NCORP: Phase III Trial of LHRH Analog Administration during Chemotherapy to Reduce Ovarian Failure following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer (S0230)Trial Description: RATIONALE: Goserelin blocks hormone production in the ovaries. It is not yet known whether ovarian suppression using goserelin will prevent ovarian failure (early menopause) in women receiving chemotherapy for breast cancer.PURPOSE: This randomized phase III trial is studying how well giving goserelin together with chemotherapy works compared with chemotherapy alone in preventing early menopause in women with stage I, stage II, or stage IIIA breast cancer. Clinical data presented in the following publication(s):PMID 25738668Disease type(s): Breast Neoplasm - Breast Cancer - InvasiveClinical Dataset(s) included:NCT00068601-D1 (PMID 25738668): There is one dataset for S0230's primary publication 25738668. This dataset contains baseline characteristics, planned chemotherapy regimen, hormone receptor status, premature ovarian failure, fertility, survival, ovarian failure, and adverse event data.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004261

• Botensilimab, an Fc-enhanced Anti-CTLA-4 Antibody, is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy

  This study explores the genomic landscape associated with a novel Fc-engineered anti-CTLA-4 antibody (botensilimab) in advanced solid tumors. We seek to understand if enhancing the Fc-region affinity of anti-CTLA-4 antibodies can improve anti-tumor efficacy and expand clinical benefit to tumors poorly responsive to conventional immunotherapy. As part of an ongoing open-label, Phase 1, multicenter study, we conducted an exploratory sub-analysis of genomics data. The primary study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of botensilimab monotherapy and in combination with an anti-PD-1 antibody (balstilimab) in participants with advanced solid tumors. RNA from formalin-fixed paraffin-embedded (FFPE) tumor biopsies and matched normal blood samples were isolated and subjected to RNA-sequencing using the Personalis ImmunoID NeXT Platform. We demonstrated that anti-CTLA-4 engineered for enhanced FcγR affinity leverages FcγR-dependent mechanisms to potentiate T cell responsiveness, reduce intratumoral Tregs, and enhance antigen presenting cell activation. This genomic analysis contributes to our understanding of the molecular mechanisms underlying patient responses to Fc-engineered anti-CTLA-4 therapy and may inform future strategies to expand the clinical benefit of immune checkpoint blockade in cancer immunotherapy.

  Study phs003704

• Open-Label, Phase I study of NeoVax with Nivolumab in Patients with Ovarian Cancer

  Personalized neoantigen-targeting cancer vaccines (PCV) in the adjuvant setting are of increasing interest across malignancies. Herein, we report the results of a first-in-disease phase I clinical trial testing the feasibility and safety of PCV for high-grade epithelial ovarian cancer (HGOC). ‘NeoVax' consisted of pools of synthetic long peptides targeting patient-specific neoantigens admixed with the immunostimulant poly-ICLC, was combined with delayed administration of anti-PD-1 antibody, and was tested in 10 patients (one newly diagnosed patient (Cohort A) and 9 patients at first recurrence (Cohort B)) with platinum-sensitive OC following standard-of-care (SOC) platinum doublet chemotherapy. Nine of 12 evaluable Cohort B patients were vaccinated (75%, 90% CI 47-93%) and 1 of 9 Cohort A patients (11%, 90% CI 0.6 – 43%). No unexpected safety signals were encountered, and no patients discontinued treatment due to toxicity. Across patients, >70% selected targets remained detectable by non-invasive cell-free DNA analysis despite a median of 6.5 months from the time of diagnostic biopsy to vaccine administration, during which patients received SOC chemotherapy. Biomarker analysis was suggestive of biologic activity of the vaccine in 6 of 10 patients and this was associated with broader tumor and vaccine-specific immune responses in blood and tumor following vaccination. Resistant tumor clones reflected diverse mechanisms affecting antigen presentation, indicative of immune-selective pressure exerted by vaccination. Overall, the interplay between the repertoire of antigens presented by the tumor and the breadth of induced immunity appeared to dictate clinical efficacy following vaccination.We are submitting:WES and WGS data from whole blood samples and tumor FFPE samplesRNA-seq data from tumor FFPE samplesscRNA-seq and scTCR-seq data from tumor biopsiesBulk TCR-seq data from CD3+ PBMC from blood samplesWGS and RNA-seq data from organoids

  Study phs004380

• BPH Tissues for Cell Culture and Analysis - A Patient-Derived Xenograft Model Using Benign Prostatic Tissues

  Our goal was to establish and characterize a patient-derived xenograft model for benign prostatic hyperplasia (BPH) using human benign prostatic tissues. Characterization of the model was done by histology, immunohistochemistry, proteomics, and transcriptome analysis (RNAseq). The RNAseq data will be deposited in dbGaP. Subjects were undergoing prostatectomy for prostate or bladder cancer, with concurrent BPH, and consented to the use of surplus tissue for research studies. The RNAseq studies included 6 patients. Phenotypic data include patient age, sex, prostate size, serum prostate-specific antigen (PSA) level, and international prostate symptom score (IPSS). Sequencing was done on an Illumina NovaSeq 6000, and data were analyzed using Kallisto. Data are submitted as raw sequencing (fastq) files.

  Study phs003692

• A Phase 1-2 Study of the Combination of Olaparib and Tremelimumab in BRCA1 and BRCA2 Mutation Carriers with Recurrent Ovarian Cancer (NCT02571725)

  INST1419: A phase 1-2 study of the combination of olaparib and tremelimumab in BRCA1 and BRCA2 mutation carriers with recurrent ovarian cancer (NCT02571725) was designed to evaluate the safety and efficacy of combined treatment with the PARP inhibitor olaparib and the CTLA4 immune checkpoint inhibitor tremelimumab in women with recurrent ovarian cancer and a germline BRCA1 or BRCA2 mutation. This was a multi-site single-arm open-label study that enrolled 50 subjects with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer between 2016 and 2020. Treatment efficacy was assessed using best overall response by modified WHO (mWHO) criteria, and secondary endpoints included disease control rate, duration of response, and progression-free and overall survival. The median age was 56 (range 39-78). All patients had measurable disease and pathogenic germline mutations in BRCA1 (72%) or BRCA2 (28%). Subjects received 300mg of olaparib by mouth, twice daily, and tremelimumab at 10mg/kg IV every four weeks for 6 doses, and then every 12 weeks for up to 24 months. Following an interim data safety monitoring review in 2018, the protocol was modified to reduce the frequency of tremelimumab infusions to 10mg/kg IV every four weeks for 4 doses, followed by infusions every 12 weeks. Exploratory biomarker assessments were performed using archived formalin-fixed paraffin-embedded (FFPE) tumor samples collected at the time of initial cytoreductive surgery from 33 subjects. Clinical characteristics and outcomes for the biomarker cohort were similar to the overall and response cohorts. Candidate biomarkers were identified based on differential gene expression in samples from patients with clinical benefit from treatment, defined as disease control for at least 12 weeks, versus those with progressive disease. For RNAseq, sample integrity was assessed using Agilent Tapestation, to ensure the DV200 was greater than or equal to 30. Sequencing was done on the Illumina NovaSeq instrument by Personalis. Gene expression used in this analysis was the normalized measure defined as transcripts per million (TPM) total RNA molecules. Welch's t-test was used to assess whether there was a difference in gene expression based on clinical benefit. The area under the receiver operating characteristic curve (AUC) was also computed for TPM gene expression based on clinical benefit. The AUC, as determined by the trapezoidal rule, was estimated by the concordance index (SAS 9.4 LOGISTIC procedure). DNA quality was confirmed if the DNA integrity number was greater than or equal to 3. Exome enrichment was performed using the Accuracy and Content Enhanced (ACE) version 4 (ACE ImmunoID NeXT) enrichment platform of Personalis. Briefly, DNA from tumor and cryopreserved PBMC samples were used to construct whole-exome capture libraries, and additional custom probes and optimized chemistry improved uniformity of coverage in sequence regions of high G-C content across the exome using ACE technology. Sequencing was performed at 20 Gigabase (G) sequencing depth for normal samples and 35G sequencing depth for tumor samples. All DNA and RNA reads were aligned to the hs37d5 reference genome built in accordance with the Personalis ACE Cancer Exome Analysis Pipeline, duplicate reads were removed, and the Genome Analysis toolkit was used to correct base quality scores and improve sequence alignment. Mutational burdens were generated using tumor-specific genomic events (SNVs, indels and fusions) of at least 5% allelic fraction that were verified using transcriptomic data. All potential neoepitopes were created for each mutation and tested for presentation, and considered putative neoepitopes if they were predicted to bind to any patient-specific alleles. The Xenium platform was used for spatial transcriptomic analyses using Xenium slides and sample prep reagents (10x Genomics). The immune panel was augmented with custom-ordered genes. Initial preprocessing included quality control, normalization, batch correction, and clustering. Cells with fewer than 20 detected features were excluded as low-quality. High-quality cell-by-gene count matrices were processed using Seurat 5.3.0, with normalization performed using SCTransform. Batch correction was carried out using Harmony integration, following standard preprocessing: individual dataset normalization, merging, PCA (RunPCA), and integration via RunHarmony. Clustering was performed on the Harmony-corrected embeddings using FindNeighbors and FindClusters (resolution = 0.03), and visualized with UMAP (RunUMAP). Cell types were initially assigned using SingleR with the HPCA reference dataset. To resolve cellular heterogeneity, subclustering was performed on select clusters using the FindSubCluster function in Seurat. Canonical marker genes used for cell type identification included CD3E for T cells, MS4A1 for B cells and EPCAM for epithelial and DCN for fibroblasts. Results from this trial demonstrated grade 3 or 4 non-hematologic toxicity in 57% of subjects. The overall response rate was 32.7% (95% CI 19.5-45.8%), with a disease control rate of 47.7% (95% CI 33.0-62.5%). In exploratory biomarker analyses, low VSTM5 or IFIT1B expression predicted treatment benefit and progression-free survival (pData available through dbGaP include RNAseq, whole exome sequencing, and Xenium spatial transcriptomic data.

  Study phs004512

• Epigenomics of Prostate Cancer from Cell Free Plasma

  We sought to perform epigenomic characterization of prostate cancers by profiling circulating nucleosomes isolated from patient plasma using cell free chromatin immunoprecipitation followed by sequencing (cfChIP-seq). Our major findings include identification of prostate-cancer specific regulatory elements using a novel statistical method accounting for variable tumor DNA fraction in plasma, inferring transcription factor activity based on binding motif enrichment within regulatory elements, and epigenetically phenotyping patients based on clinical and genomic features. Data available in dbGaP will include cfChIP-seq and targeted sequencing from approximately 50 patients with a known diagnosis of cancer and healthy patient controls.

  Study phs003482

• HINTS Geo-Coded Data 2017 (HINTS 5 Cycle 1)

  The Health Information National Trends Survey (HINTS) is a nationally representative survey which has been administered every few years by the National Cancer Institute since 2003. HINTS 5 includes four data collection cycles over the course of four years. The first round of data collection for HINTS 5 (Cycle 1) was conducted from January 25 through May 5, 2017 with a goal of obtaining 3,500 completed questionnaires, with a final sample including 3,285 respondents.

  Study phs004210

• WGS of Five Pancreatic Cancer Patients-Tumor and Normal

  We performed whole genome sequence on tumor-derived and normal cell lines from patients who had terminal pancreatic cancer and consented for rapid autopsy upon their death. The 5 samples are from Dr. Christine Iacobuzio-Donahue's rapid autopsy program as reported in Boland et al. (PLOSOne, 2024, In Press, PMID 38352348).

  Study phs003775

• Luminal Androgen Receptor-Enriched Triple Negative Breast Cancer

  This is a study to determine the efficacy of androgen receptor (AR) inhibitors in LAR (luminal androgen receptor)-enriched triple-negative breast cancer (TNBC) in the neoadjuvant setting. Twenty-four patients were treated with neoadjuvant AR inhibitor enzalutamide and paclitaxel for 12 weeks. Whole exome sequencing and RNA-sequencing was performed prior to treatment. The data for only two patients are consented for release through dbGaP. The remaining data are available under a Materials Transfer Agreement with the University of Texas MD Anderson Cancer Center.

  Study phs003586