A5022120876- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Axon Guidance and Neuronal Signaling
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- CAR-T cell therapy research
- Neuroblastoma Research and Treatments
- Immunotherapy and Immune Responses
- Tryptophan and brain disorders
- Hematopoietic Stem Cell Transplantation
- Cancer, Hypoxia, and Metabolism
- Hedgehog Signaling Pathway Studies
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Renal Transplantation Outcomes and Treatments
- Nanoparticle-Based Drug Delivery
- Immune Cell Function and Interaction
- Cancer, Lipids, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- vaccines and immunoinformatics approaches
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Liver physiology and pathology
Johns Hopkins Medicine
2017-2023
Johns Hopkins University
2017-2023
Sidney Kimmel Comprehensive Cancer Center
2017-2023
Sidney Kimmel Cancer Center
2018-2022
Maryland Oncology Hematology
2020
University of Baltimore
2019
Bloomberg (United States)
2018
Johns Hopkins Hospital
2017
Abstract How tumor-associated macrophages transit from a predominant antitumor M1-like phenotype to protumoral M2-like during the development of pancreatic ductal adenocarcinoma (PDA) remains be elucidated. We thus conducted study by employing PDA-macrophage co-culture system, an “orthotopic” PDA syngeneic mouse model, and human specimens, together with derived GARP knockout mice multiple analytic tools including whole-genome RNA sequencing, DNA methylation arrays, multiplex...
The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 CCR5 were induced in PDAC following treatment with anti-PD-1 antibody (αPD-1); thus, we examined vaccine or radiation therapy (RT) as T cell priming mechanisms together BMS-687681, a dual antagonist (CCR2/5i), combination αPD-1 new strategies. Using mouse models, demonstrated RT followed...
Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid has had limited success. Here, we sought to target through modifying specific stromal component.A murine model metastatic PDAC treated with an irradiated whole-cell vaccine and specimens from patients same type were used assess immune-modulating effect hyaluronan (HA) degradation by PEGPH20.Targeting degrading HA PEGPH20 in combination...
Pancreatic ductal adenocarcinoma (PDAC) represents an immune quiescent tumor that is resistant to checkpoint inhibitors. Previously, our group has shown a GM-CSF–secreting allogenic pancreatic cell vaccine (GVAX) may prime the microenvironment by inducing intratumoral T infiltration. Here, we show untreated PDACs express minimal indoleamine-2,3-dioxygenase (IDO1); however, GVAX therapy induced IDO1 expression on epithelia as well vaccine-induced tertiary lymphoid aggregates. plays role in...
<h3>Background</h3> Immune checkpoint inhibitors are not effective for pancreatic ductal adenocarcinoma (PDAC) as single agents. Vaccine therapy may sensitize PDACs to inhibitor treatments. Annexin A2 (ANXA2) is a pro-metastasis protein, previously identified relevant PDAC antigen that expressed by GM-CSF-secreting allogenic whole tumor cell vaccine (GVAX) induce an anti-ANXA2 antibody response in patients with PDAC. We hypothesized ANXA2-targeting approach only provokes immune but also...
<h3>Background</h3> The pancreatic cancer vaccine, GVAX, induces novel lymphoid aggregates in the otherwise immune quiescent ductal adenocarcinoma (PDAC). GVAX also upregulates PD-1/PD-L1 pathway, and a pre-clinical model demonstrated anti-tumor effects of combination anti-PD-1 antibody therapy (GVAX/αPD-1). Resistance to was associated with an immune-suppressive myeloid cell infiltration, which may limit further therapeutic gains GVAX/αPD-1 therapy. expression CSF-1R, receptor important for...
Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity further how affects response by regulating myeloid cells...
Noninfectious fevers are common early after T cell-replete HLA haploidentical (haplo) peripheral blood transplants and have been associated with cytokine release syndrome overall mortality. However, less is known regarding the incidence associations of fever bone marrow transplantation (BMT) post-transplant cyclophosphamide (PTCy). We hypothesized that would be myeloablative conditioning (MAC), because its relative increase in tissue damage augmenting antigen presentation class II...
Background Radiation therapy (RT) has the potential to enhance efficacy of immunotherapy, such as checkpoint inhibitors, which dramatically altered landscape treatments for many cancers, but not yet pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) were induced on tumor epithelia PDACs following neoadjuvant including RT, suggesting RT may prime PDAC PD-1 blockade antibody (αPD-1) or IDO1 inhibitor (IDO1i)...
Pancreatic ductal adenocarcinoma (PDAC) is in urgent need of better diagnostic and therapeutic methods due to its late diagnosis, limited treatment options poor prognosis. Finding the right animal models recapitulate tumor molecular pathogenesis microenvironment (TME) complexity critical for preclinical immunotherapeutic non-immunotherapeutic developments. In this review, we summarize evaluate popular including patient-derived xenograft models, humanized mouse genetically engineered...
Metastatic colorectal cancer (CRC) is poorly immunogenic, with limited neoantigens that can be targeted by vaccine. Previous approaches to upregulate neoantigen have had success. In this study, we investigated the role of a DNA methyltransferase inhibitor (DNMTi), 5-aza-2'-deoxycytidine (DAC), in inducing testis antigen (CTA) expression and evaluated antitumor efficacy combinatorial approach an epigenetically regulated vaccine EpiGVAX DAC. A murine model metastatic CRC treated combination...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most chemotherapy- and radiotherapy-resistant tumors. The c-Met Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory in primary tumor growth metastases formation. Targeting both HGF/c-Met Hh has promising results preclinical studies; however, benefits were not readily translated into clinical trials with PDAC patients. In this study, utilizing mouse models PDAC, we showed that inhibition either or...
Pancreatic adenocarcinoma (PDA) is characterized by a dense desmoplastic reaction that comprises 60-90% of the tumor, while only 10-40% tumor composed malignant epithelial cells. This stromal fibroblast cells, extracellular matrix proteins, and immune Accumulating evidence has suggested cell compartments interact during pathogenesis this disease. Therefore, it important to identify signaling pathways responsible for interaction better understand mechanisms which PDA invades metastasizes....
ABSTRACT Axon guidance molecules were found to be the gene family most frequently altered in pancreatic ductal adenocarcinoma (PDA) through mutations and copy number changes. However, exact molecular mechanism regarding PDA development remained unclear. Using genetically engineered mouse models examine one of axon molecules, semaphorin 3D (SEMA3D), we a dual role for tumor-derived SEMA3D malignant transformation epithelial cells nerve-derived development. This was demonstrated by...
Background: We hypothesized that, early after HLA-haploidentical (haplo) bone marrow transplant (BMT), donor CD4+ T cell recognition of allogeneic HLA class II molecules results in the secretion pyrogenic cytokines and delivery "help" to anti-tumor effector cells. also postulated that mismatched host stimulate fever effects proportion their level expression polymorphism (i.e. HLA-DRB1 > DPB1 or DQB1). Methods: retrospectively analyzed association fever, defined as temperature ≥38.3 once...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a devastating malignant disease. Upon diagnosis, eighty percent of patients present with metastatic Perineural invasion, the spreading cancer to space surrounding or invading nerve, often found in surgically removed pancreatic tumors and associated worse overall prognosis including high risk recurrence metastasis. invasion thought represent initial steps metastasis; however, mechanism that mediates role neurons precancerous inflammation...
Abstract Bispecific T cell engager (BiTE®) antibody constructs are designed to redirect cells induce lysis of tumor through simultaneous binding CD3 on and a associated antigen. BiTE® have previously been shown be effective at depleting blood tissue targets in B malignancies, suggesting therapeutic potential for solid tumors. Pancreatic ductal adenocarcinoma (PDA) is devastating malignant disease with dismal prognosis even currently available therapies. The differentiation antigen mesothelin...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a devastating disease, with the lowest stage-combined 5-year survival rate of any cancer type at 8%. One major attribute for this poor prognosis lack effective treatments in preventing and controlling metastasis. Previously, our lab has identified secreted protein Semaphorin3D (Sema3D) to be involved invasion metastasis PDA. Sema3D part axon guidance gene family, recently been reported most frequently altered family We have previously found...
<p>Supplemental Data: Figure S1: Pathologic representation of hemispleen liver metastases; S2: Treatment schema; S3: Supplemental survival; S4: FACS PD1/PDL1 expression; S5: Myeloid cell FACS; S6: Multiplex IHC myeloid and HA high/low; S7: CXCR4 S8: RNAseq PD1/PDL1</p>
<div>AbstractPurpose:<p>Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid has had limited success. Here, we sought to target through modifying specific stromal component.</p>Experimental Design:<p>A murine model metastatic PDAC treated with an irradiated whole-cell vaccine and specimens from patients same type were used assess immune-modulating effect hyaluronan (HA)...
<div>AbstractPurpose:<p>Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid has had limited success. Here, we sought to target through modifying specific stromal component.</p>Experimental Design:<p>A murine model metastatic PDAC treated with an irradiated whole-cell vaccine and specimens from patients same type were used assess immune-modulating effect hyaluronan (HA)...
<p>Supplemental Data: Figure S1: Pathologic representation of hemispleen liver metastases; S2: Treatment schema; S3: Supplemental survival; S4: FACS PD1/PDL1 expression; S5: Myeloid cell FACS; S6: Multiplex IHC myeloid and HA high/low; S7: CXCR4 S8: RNAseq PD1/PDL1</p>