A5013431516- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Extracellular vesicles in disease
- Nanoplatforms for cancer theranostics
- Melanoma and MAPK Pathways
- Ovarian cancer diagnosis and treatment
- COVID-19 and healthcare impacts
- PARP inhibition in cancer therapy
- Immune cells in cancer
- Bladder and Urothelial Cancer Treatments
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Cancer, Stress, Anesthesia, and Immune Response
- Cutaneous Melanoma Detection and Management
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Computational Drug Discovery Methods
University of Pennsylvania
2019-2025
California University of Pennsylvania
2024
Abramson Cancer Center
2023
Sidney Kimmel Cancer Center
2023
University of Pennsylvania Health System
2023
Cancer Research Center
2019
BackgroundOnly a minority of melanoma patients experience durable responses to immunotherapies due inter- and intra-tumoral heterogeneity in melanoma. As result, there is pressing need for suitable preclinical models investigate resistance mechanisms enhance treatment efficacy.MethodsHere, we report two different methods generating patient-derived organoids (MPDOs), one embedded collagen gel, the other inlaid Matrigel. MPDOs Matrigel are used assessing therapeutic effects anti-PD-1...
Macrophages play a pivotal role in tumor immunity. We report that reprogramming of macrophages to tumor-associated (TAMs) promotes the secretion exosomes. Mechanistically, increased exosome is driven by MADD, which phosphorylated Akt upon TAM induction and activates Rab27a. exosomes carry high levels programmed death-ligand 1 (PD-L1) potently suppress proliferation function CD8
Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells. PDGFR transmembrane domain delivers DR5-scFvs to sEVs. DR5-scFv rapidly induce apoptosis different types + cancer cells, myeloid-derived suppressor cells (MDSCs), and cancer-associated fibroblasts (CAFs). migrate specifically tumors in vitro vivo....
Abstract Purpose: Neoadjuvant anti-PD1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TILs), and more TILs are associated with better treatment response. A major pathological response (MPR) after neoadjuvant usually comprises tumor necrosis fibrosis. The role of necrotic (nTILs) has not been explored. Experimental Design: We performed CD3 CD8 immunohistochemical stains on 41 melanomas geographic necrosis. 14 were immunotherapy-naïve, 27 had treated one dose anti-PD-1 two...
The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field immuno-oncology as well revealed limitations current treatments, majority patients do not respond to immunotherapy. Development accurate preclinical models quickly identify novel effective therapeutic combinations are critical address this unmet clinical need. Pancreatic ductal (PDA) is a canonical example an resistant tumor with only 2% responding genetically engineered...
The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field immuno-oncology as well revealed limitations current treatments, majority patients do not respond to immunotherapy. Development accurate preclinical models quickly identify novel effective therapeutic combinations are critical address this unmet clinical need. Pancreatic ductal (PDA) is a canonical example an resistant tumor with only 2% responding genetically engineered...
<title>Abstract</title> Melanoma is a common and aggressive cancer, with rising incidence in most developed countries. Major discoveries melanoma biology have been rapidly translated, allowing cures for some late-stage patients. Despite these advances, incomplete knowledge of genes pathways that are gained or lost during melanogenesis prohibits many To identify gain-of-function loss-of-function drivers melanoma, we established multi-omics cohort patient-derived xenografts. By linking...
<div>AbstractPurpose:<p>Neoadjuvant anti–PD-1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TIL), and more TIL are associated with better treatment response. A major pathologic response (MPR) after neoadjuvant usually comprises tumor necrosis fibrosis. The role of necrotic (nTIL) has not been explored.</p>Experimental Design:<p>We performed CD3 CD8 IHC stains on 41 melanomas geographic necrosis. Of the 41, 14 were immunotherapy-naïve, 27 had treated...
<p>All supplemental data (Supp Figs S1-S4)</p>
Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism humans remains unclear. We performed multimodal analysis across time 32 stage IV melanoma patients treated anti-PD-1, anti-CTLA-4, or + (combination) therapy. Anti-CTLA-4 induced more durable immune responses than whereas combination therapy mobilized greater sustained responses. developed algorithm Cyclone to track temporal clonal dynamics...
e21503 Background: Immune checkpoint inhibitor (ICI) therapy for advanced melanoma in the first-line setting often results durable responses and prolonged overall survival (OS) after achieving a complete response (CR). While generally well-tolerated, there are financial toxicities treatment related adverse events (TRAEs) associated with ICI use. There limited data to inform optimal duration of CR, how specific patient factors may lead variable OS patients (pts) CR. Methods: Pts locally stage...
<h3>Background</h3> Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism humans remains unclear. A better understanding of cellular molecular mechanisms αPD-1 αCTLA-4 individually, combination, will guide development safer more effective combination immunotherapy strategies. <h3>Methods</h3> We performed multimodal (scRNA + TCR epitope) analysis across time 32 stage IV melanoma patients treated...
Abstract Over the last few years, we have gained insights into how immunotherapy, including checkpoint blockade, modulates key CD4 and CD8 T cell subsets in anti-tumor immunity. This information can now give us immunotherapy impact immunity setting of COVID-19. Indeed, recently demonstrated that cancer patients with depletion high COVID-19 mortality despite adequate B antibody production, highlighting importance cellular Conversely, by anti-CD20 therapy, cells compensate for impaired humoral...