A5078692994- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Esophageal Cancer Research and Treatment
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Genetic factors in colorectal cancer
- Neuroendocrine Tumor Research Advances
- Cancer, Hypoxia, and Metabolism
- Colorectal and Anal Carcinomas
- Cancer Research and Treatments
- Gastric Cancer Management and Outcomes
- Neuroblastoma Research and Treatments
- Economic and Financial Impacts of Cancer
- Colorectal Cancer Surgical Treatments
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Diagnosis and Treatment
- Gallbladder and Bile Duct Disorders
- Immune cells in cancer
- Hepatocellular Carcinoma Treatment and Prognosis
University Hospitals of Cleveland
2004-2025
University Hospitals Seidman Cancer Center
2018-2025
Case Western Reserve University
2004-2025
University of Pennsylvania
2006-2023
Cancer Research Institute
2012-2023
Case Comprehensive Cancer Center
2020-2023
Twitter (United States)
2022-2023
University School
2020
UPMC Hillman Cancer Center
2014
Moffitt Cancer Center
2006-2007
The cell-surface molecule CD40 activates antigen-presenting cells and enhances immune responses. is also expressed by solid tumors, but its engagement results in apoptosis. CP-870,893, a fully human selective agonist monoclonal antibody (mAb), was tested for safety phase I dose-escalation study.Patients with advanced tumors received single doses of CP-870,893 intravenously. primary objective to determine the maximum-tolerated dose (MTD). Secondary objectives included assessment modulation...
Disabling the function of immune checkpoint molecules can unlock T-cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. To date, pancreatic carcinoma is fully refractory to these antibodies. Here, using a genetically engineered mouse model ductal adenocarcinoma in which spontaneous minimal, we found PD-L1 prominent tumor microenvironment, phenotype confirmed...
KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy sotorasib, a G12C inhibitor, previously treated patients with p.G12C–mutated cancer are unknown.
CD40 activation is a novel clinical opportunity for cancer immunotherapy. Despite numerous active trials with agonistic monoclonal antibodies (mAb), biological effects and treatment-related modulation of the tumor microenvironment (TME) remain poorly understood.
Neutrophil Extracellular Traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens causes tissue damage in diseases. Whether NETs can cancer cells is unexplored. Here, we report that combination glutaminase inhibitor CB-839 5-FU inhibits the growth PIK3CA mutant colorectal cancers (CRCs) xenograft, syngeneic, genetically engineered mouse models part through NETs. Disruption by either DNase I treatment or depletion neutrophils CRCs...
In carcinogen-driven cancers, a high mutational burden results in neoepitopes that can be recognized immunologically. Such carcinogen-induced tumors may evade this immune response through “immunoediting,” whereby adapt to pressure and escape T cell–mediated killing. Many lack neoepitope burden, it remains unclear whether immunoediting occurs such cases. Here, we evaluated cell immunity an autochthonous mouse model of pancreatic cancer found low absence predicted derived from tumor mutations,...
Abstract Most cancer-associated deaths result from metastasis. However, it remains unknown whether the size, microenvironment or other features of a metastatic lesion dictate its behaviour determine efficacy chemotherapy in adjuvant (micrometastatic) setting. Here we delineate natural history metastasis an autochthonous model pancreatic ductal adenocarcinoma (PDAC), using lineage tracing to examine evolution disseminated cancer cells and their associated microenvironment. With increasing...
We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four previously untreated checkpoint blockade were enrolled. The agonistic CP-870,893 the tremelimumab dosed concomitantly every 3 weeks 12 weeks, respectively, across four dose combinations. Two developed dose-limiting grade immune-mediated colitis that led to definition maximum tolerated (MTD)....
Abstract PIK3CA encodes the p110α catalytic subunit of PI3K and is frequently mutated in human cancers, including ∼30% colorectal cancer. Oncogenic mutations render cancers more dependent on glutamine. Here we report that glutaminase inhibitor CB-839 preferentially inhibits xenograft growth PIK3CA-mutant, but not wild-type (WT), cancers. Moreover, combination 5-fluorouracil (5-FU) induces PIK3CA-mutant tumor regression models. treatment increased reactive oxygen species caused nuclear...
360490 Background: KRAS mutation is present in 90% of pancreatic ductal adenocarcinomas with p.G12C accounting for 1% to 2% these mutations. Sotorasib, a small molecule that specifically and irreversibly inhibits G12C , has been investigated the CodeBreaK100 trial patients -mutated advanced solid tumors. Herein, we report on largest dataset evaluating efficacy safety inhibitor pretreated cancer. Methods: (NCT03600883) an international, single arm, phase I/II study sotorasib tumors ≥ 1 prior...
TRX518 is a mAb engaging the glucocorticoid-induced TNF receptor-related protein (GITR). This open-label, phase I study (TRX518-003) evaluated safety and efficacy of repeated dose monotherapy in combination with gemcitabine, pembrolizumab, or nivolumab advanced solid tumors.
Abstract Cancer immunotherapies are increasingly effective in the clinic, especially immune checkpoint blockade delivered to patients who have T cell–infiltrated tumors. Agonistic CD40 mAb promotes stromal degradation and, combination with chemotherapy, drives cell infiltration and de novo responses against tumors, rendering resistant tumors susceptible current immunotherapies. Partnering anti-CD40 different treatments is an attractive approach for next phase of cancer immunotherapies, a...
// Erryk S. Katayama 1 , Jonathan J. Hue 2 David L. Bajor 3 4 Lee M. Ocuin 5 John B. Ammori Jeffrey Hardacre and Jordan Winter Department of Surgery, Case Western Reserve University School Medicine, Cleveland, Ohio, USA Hospitals Seidman Cancer Center Comprehensive Center, Division Hematology Oncology, Hepatobiliary Pancreatic Atrium Health, Charlotte, North Carolina, Correspondence to: Winter, email: Jordan.Winter@UHhospitals.org Keywords: pancreatic cancer; ductal adenocarcinoma; clinical...
PURPOSE Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is standard first-line therapy for mPC patients with favorable performance status good organ function. In phase I study, devimistat (CPI-613) in combination modified FFX (mFFX) was deemed safe exhibited promising efficacy mPC. METHODS The AVENGER 500 trial (ClinicalTrials.gov identifier: NCT03504423 ) global, randomized III conducted at 74 sites...
This was the first phase 1 study conducted in United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion B), investigating safety preliminary efficacy toripalimab (anti-programmed cell death-1 inhibitor) patients with advanced malignancies. Patients malignancies that progressed after treatment at least one prior line standard systemic therapy, including advanced/recurrent cholangiocarcinoma (CCA), received 240 mg every 3 weeks part B. The...
836 Background: Circulating tumor DNA (ctDNA) has a short half-life (<2 hours) which may permit real-time monitoring of status. This single-institution study aimed to assess the feasibility rapid treatment response evaluation through serial short-interval ctDNA testing. Methods: Patients with gastrointestinal (GI) cancer undergoing immune checkpoint inhibitor (ICI)-based therapy were included. A personalized, tumor-informed assay (Signatera, Natera, Inc.) was used in this study. We...
TPS843 Background: Black individuals, including African Americans, experience a disproportionate cancer burden and exhibit the lowest survival rates among all racial groups for gastrointestinal (GI) cancers. The EQUITY GI study seeks to address significant health disparities encountered by patients with cancers in areas of biomarker testing, evidence-based care, clinical trial participation, literacy. Our central hypothesis postulates that comprehensive approach—encompassing appropriate...
7 Background: Mitomycin (MMC) is used concurrently during chemoradiation (CRT) treatment for non-metastatic anal squamous cell carcinoma (SCCA). The most effective dosing of MMC not established, and due to concerns tolerability, many have adopted a dose-reduction strategy. This study evaluates differences in response recurrence between this setting. Methods: Demographics, age, smoking history, staging, history were collected patients with SCCA treated CRT from January 2011-September 2024 at...
644 Background: There is limited data to guide surveillance in biliary tract cancers (BTCs) following resection. Minimal residual disease (MRD) assays utilize circulating tumor DNA (ctDNA) detect early recurrence. Current on the use of ctDNA conjunction with imaging. In this study, we aim elucidate role monitoring patients who have undergone curative Methods: We conducted a retrospective search at tertiary care and several satellite settings identify BTCs underwent surgery subsequently had...
8 Background: Advanced-stage squamous cell carcinoma of the anus (aSCCA) is a rare malignancy. Diagnostic biopsies are often inadequate for tissue-based genomic profiling, thus profiles largely unexplored in this setting. We assessed liquid biopsy NGS results aSCCA patients (pts) and described by age sex. To our knowledge, we first to describe genetic alterations patient population. Methods: Pts with who underwent circulating tumor DNA (ctDNA) Guardant360 assays from 2017 2024 were included....
TPS794 Background: Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis, with 34% 5-year survival rate for patients localized disease. Guidelines recommend consideration of neoadjuvant approaches in PDA the goals controlling microscopic metastatic disease and increasing rates microscopically margin-negative resections. One hallmark characteristics is micronutrient poor, highly stromal microenvironment. Surviving this environment requires enhanced mitochondrial function, which...
TPS516 Background: Esophageal adenocarcinoma (EAC) is the seventh most common cancer globally and ranks sixth in overall mortality. Despite improvements pre-operative therapy, EAC has a high recurrence rate, especially among patients whose tumors do not achieve pathologic complete response (pCR), thus there critical need to enhance pCR rate improve long-term outcomes. We recently discovered that subset of EACs are driven by tumor-intrinsic oncogenic TGFβ signaling have identified two...