A5073582280- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic and Hepatic Oncology Research
- Advanced Breast Cancer Therapies
- Neuroendocrine Tumor Research Advances
- Electrolyte and hormonal disorders
- Diet and metabolism studies
- Pharmacological Effects and Toxicity Studies
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Extracellular vesicles in disease
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Ferroptosis and cancer prognosis
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Sarcoma Diagnosis and Treatment
- Diabetes and associated disorders
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Lung Cancer Treatments and Mutations
- Radiomics and Machine Learning in Medical Imaging
- Cancer Research and Treatments
Agenus (United States)
2021-2025
Hadassah Medical Center
2025
Deciphera Pharmaceuticals (United States)
2024
Bayer (United States)
2023
Beth Israel Deaconess Medical Center
2018-2022
Harvard University
2019-2022
Beth Israel Deaconess Hospital
2020-2021
Brown University
2013
Rhode Island Hospital
2013
Massachusetts General Hospital
1994
Abstract Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed expand therapy cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) being evaluated in ongoing expanded phase 1 study. The primary endpoint...
PURPOSE Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was define the safety efficacy botensilimab (BOT), an Fc-enhanced anti–cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), anti–PD-1 in sarcomas. METHODS BOT administered intravenously (IV) at 1 mg/kg or 2 once every 6 weeks combination BAL IV 3 up years. primary end point determine dose-limiting toxicities during...
Patient-derived organoid models are proving to be a powerful platform for both basic and translational studies. Here we conduct methodical analysis of pancreatic ductal adenocarcinoma (PDAC) tumor drug response in paired patient-derived xenograft (PDX) PDX-derived (PXO) grown under WNT-free culture conditions. We report specific relationship between area the curve value dose vivo growth, irrespective treatment. In addition, analyzed glycome PDX PXO demonstrate that PXOs recapitulate glycan...
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments limited by toxicity. The HOPE trial (Harnessing Organoids PErsonalized Therapy) was pilot feasibility aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC test their drug sensitivity correlation clinical outcomes. Experimental Design: PDOs were established heterogeneous...
LBA8 Background: BOT promotes optimized T cell priming, activation and memory formation by strengthening antigen presenting cell/T co-engagement. As an Fc-enhanced next-generation anti–CTLA-4 antibody, also intratumoral regulatory depletion reduces complement fixation. We present results from patients with MSS CRC treated + BAL in expanded phase 1a/1b study; NCT03860272. Methods: Patients (pts) metastatic received 1 or 2 mg/kg every 6 weeks (Q6W) 3 weeks. Crossover monotherapy to combination...
Abstract Conventional immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) elicit durable survival but primarily in patients with immune-inflamed tumors. Although the mechanisms underlying response to anti–CTLA-4 remain poorly understood, Fc-gamma receptor (FcγR) IIIA coengagement seems critical for activity, potentially explaining modest clinical benefits of approved antibodies. We demonstrate that engineered enhanced FcγR affinity leverages FcγR-dependent...
Background Tumor-specific cytotoxic T cells and cell receptors are effective tools for cancer immunotherapy. Most efforts to identify them rely on known antigens or lymphocytes that have infiltrated into the tumor bed. Approaches empirically tumor-targeting by exploiting all expressed surfaces not well developed most carcinomas, including pancreatic cancer. Methods Autologous organoids were stimulated with from patients’ peripheral blood 2 weeks generate organoid-primed (opT) cells. opT...
In pancreatic ductal adenocarcinoma cancer (PDAC) drug resistance is a severe clinical problem and patients relapse within few months after receiving the standard-of-care chemotherapy. One contributing factor to treatment desmoplastic nature of PDAC; tumours are surrounded by thick layers stroma composing up 90% tumour mass. This stroma, which mostly comprised extracellular matrix (ECM) proteins, secreted cancer-associated fibroblasts (CAFs) residing in microenvironment. However, mechanistic...
23 Background: BOT is an Fc-enhanced, multifunctional anti-CTLA−4 antibody designed to improve Fc gamma receptor-mediated effector functions and extend the reach of I-O tumor types such as MSS mCRC. Here we present preliminary data from a randomized, open-label, phase 2 study in patients (pts) with mCRC NLM treated ± BAL (anti-PD−1; NCT05608044). The aimed inform dose contribution components based on primary endpoint objective response rate (ORR) by RECIST 1.1 per investigator, safety, was...
Abstract Effective therapy options for patients (pts) with hepatocellular carcinoma (HCC) who progress on or after first-line immunotherapy (I-O) are limited. Botensilimab (BOT) is an Fc-enhanced, multifunctional CTLA-4 inhibitor differentiated mechanisms of action designed to extend cold poorly immunogenic solid tumors. BOT alone when combined balstilimab (BAL; PD-1 comparable other inhibitors) has demonstrated durable responses across 9 different treatment-refractory tumors, including...
11501 Background: Doxorubicin (DOX) is the standard of care for unresectable soft tissue sarcomas (STS). DOX induces immunogenic cell death in numerous preclinical models. Immune checkpoint inhibitors (ICIs) including antibodies (ab) to PD-1 and CTLA-4 have shown modest activity, but most STS are immune “cold” tumors do not respond. We hypothesized that concurrent would improve immunogenicity boost efficacy ICIs, anti-CTLA-4 ab zalifrelimab (ZAL) anti-PD-1 balstilimab (BAL). Methods:...
ABSTRACT Pancreatic cancer has the worst prognosis of all common tumors. Earlier diagnosis could increase survival rates and better assessment metastatic disease improve patient care. As such, there is an urgent need to develop biomarkers diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using ‘liquid biopsies’ offers attractive approach monitor status. However, it important differentiate EV-associated proteins enriched in patients with pancreatic ductal...
Melanoma characteristically grows within the epidermis along dermal-epidermal junction, sometimes extending outward up to several centimeters beyond foci of invasive tumors. Although follicular involvement by malignant melanoma is widely recognized, authors' knowledge no previously published data address this phenomenon.To examine growth characteristics in situ melanomas relation hair follicle microanatomy, authors analyzed 100 cases primary cutaneous (61 and 39 with significant components)...
Pancreatic cancer has the worst prognosis of all common tumors. Earlier diagnosis could increase survival rates and better assessment metastatic disease improve patient care. As such, there is an urgent need to develop biomarkers diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using ‘liquid biopsies’ offers attractive approach monitor status. However, it important differentiate EV-associated proteins enriched in patients with pancreatic ductal...
<h3>Background</h3> AGEN1181 is a novel anti-CTLA-4 antibody with enhanced FcyR-dependent functionality, engineered to bind high and low binding alleles of FcyRIIIA, promoting superior T cell priming, memory responses, depletion intratumoral regulatory cells. Further, avoids complement recruitment, predictive better tolerability. Here we report initial safety efficacy findings from phase I/Ib study as monotherapy in combination balstilimab (BAL; anti-PD-1). <h3>Methods</h3> Eligible patients...
<h3>Background</h3> Botensilimab is a novel fragment crystallizable (Fc)-enhanced anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody designed to promote superior immune activation and tumor killing relative first-generation IgG1 CTLA-4 antibodies. In patients with advanced solid tumors, botensilimab ± balstilimab (anti-PD-1), demonstrated durable clinical responses across nine different immunotherapy-resistant or poorly immunogenic types. The deep broad activity observed attributed its...
Pancreatic cancer has the worst prognosis of all common tumors. Earlier diagnosis could increase survival rates and better assessment metastatic disease improve patient care. As such, there is an urgent need to develop biomarkers diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using ‘liquid biopsies’ offers attractive approach monitor status. However, it important differentiate EV-associated proteins enriched in patients with pancreatic ductal...
To assess the preclinical efficacy, clinical safety and MTD of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma (PDAC).Preclinical activity was tested patient-derived xenograft (PDX) models PDAC. In open-label, phase I study, dose-escalation cohort received oral initially at 75 mg/day (range, 50‒125 mg/day; modified 3+3 design; 3/1 schedule); intravenous administered weekly for 3 weeks/28-day cycle 100‒125 mg/m2. The dose-regimen cohorts (3/1...