A5040750947- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
- Phagocytosis and Immune Regulation
- Hematopoietic Stem Cell Transplantation
- Radiomics and Machine Learning in Medical Imaging
- Virus-based gene therapy research
- Hepatocellular Carcinoma Treatment and Prognosis
- RNA Interference and Gene Delivery
- Esophageal Cancer Research and Treatment
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- PARP inhibition in cancer therapy
- Inflammatory mediators and NSAID effects
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer, Hypoxia, and Metabolism
University of Pennsylvania
2016-2025
California University of Pennsylvania
2013-2025
University of Pennsylvania Health System
2025
Parker Institute for Cancer Immunotherapy
2016-2024
Abramson Cancer Center
2007-2024
Sidney Kimmel Cancer Center
2021-2024
Cancer Research Institute
2013-2023
Cancer Research Institute of the Slovak Academy of Sciences
2007-2023
Palmetto Hematology Oncology
2009-2023
UPMC Hillman Cancer Center
2010-2023
CD40 immunotherapy shows efficacy in treating pancreatic cancer mice and humans by eliciting antitumor immunity.
Abstract The dynamics of cancer immunosurveillance remain incompletely understood, hampering efforts to develop immunotherapy cancer. We evaluated the evolving in vivo immune response a spontaneous tumor genetically defined mouse model pancreatic ductal adenocarcinoma from inception preinvasive disease invasive observed prominent leukocytic infiltration even around lowest grade lesions, but immunosuppressive cells, including tumor-associated macrophages, myeloid-derived suppressor cells...
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...
Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients who were hospitalized for COVID-19, hematologic had higher relative to solid cancer. two additional cohorts, flow cytometric serologic analyses demonstrated without similar phenotype during acute whereas impairment B cells severe respiratory syndrome 2 (SARS-CoV-2)-specific antibody responses. Despite impaired...
Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal (CASC) are heterogeneous population that provides both negative positive signals for cell growth metastasis. Fibroblast activation protein (FAP) is marker major subset CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent prognostic factor multiple types human malignancies. Prior studies established depletion FAP(+) inhibits by...
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...
This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunologic correlatives, and antitumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine patients advanced pancreatic ductal adenocarcinoma (PDA).Twenty-two chemotherapy-naïve PDA were treated 1,000 mg/m(2) once weekly for three weeks infusion CP-870,893 at 0.1 or 0.2 mg/kg on day each 28-day cycle.CP-870,893 was well-tolerated; one dose-limiting...
Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR cells ineffective for solid tumors date. We found the cell-surface molecule c-Met was expressed ∼50% breast tumors, prompting construction a cell specific c-Met, which halted tumor growth immune-incompetent mice with xenografts. then evaluated safety and feasibility treating metastatic cancer intratumoral administration...
Abstract Recent success in cancer immunotherapy has reinvigorated the hypothesis that immune system can control many if not most cancers, some cases producing durable responses a way seen with small-molecule drugs. Agonistic CD40 monoclonal antibodies (mAb) offer new therapeutic option which potential to generate anticancer immunity by various mechanisms. is TNF receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B and monocytes well...
Myeloid-derived suppressor cells (MDSCs) dampen the immune response thorough inhibition of T cell activation and proliferation often are expanded in pathological conditions. Here, we studied fate MDSCs cancer. Unexpectedly, had lower viability a shorter half-life tumor-bearing mice compared with neutrophils monocytes. The reduction MDSC was due to increased apoptosis, which mediated by expression TNF-related apoptosis–induced ligand receptors (TRAIL-Rs) these cells. Targeting TRAIL-Rs naive...
CD25 monoclonal antibody therapy rapidly and durably depletes T regs in cancer patients through a mechanism consistent with reprogramming.