A5087804855- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Veterinary Oncology Research
- CAR-T cell therapy research
- Toxoplasma gondii Research Studies
- Molecular Biology Techniques and Applications
- NF-κB Signaling Pathways
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Immune Response and Inflammation
- Infectious Diseases and Mycology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Adhesion Molecules Research
- Biomedical and Engineering Education
- Xenotransplantation and immune response
- Platelet Disorders and Treatments
- Lymphoma Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Parathyroid Disorders and Treatments
University of Pennsylvania
2016-2025
Parker Institute for Cancer Immunotherapy
2018-2022
Advanced Pharma
2022
Penn Center for AIDS Research
2021
NHS Lothian
2021
Philadelphia University
2021
The Ohio State University
2016
California University of Pennsylvania
2015
South University
2012
University of North Carolina at Chapel Hill
2011
The updated VCOG-CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 published within Veterinary Comparative Oncology 2016. As Cooperative Group (VCOG) is no longer an active entity, original authors contributors to v1.0 v1.1 were consulted for input, additional co-authors sought expansion refinement of adverse event (AE) categories. includes expanded neurology, cardiac immunologic AE sections, addition procedural-specific...
Different members of the Rel/NF-κB family may play different roles in immunity and inflammation. We report here that c-Rel–deficient mice are resistant to autoimmune encephalomyelitis defective Th1, but not Th2 responses. The Th1 deficiency appears be caused by selective blockade IL-12 production antigen-presenting cells, as well a complete abrogation IFN-γ expression T cells. Interestingly, c-Rel does affect T-bet expression, suggesting act downstream during cell differentiation. Thus,...
Recombinant Listeria vaccines induce tumor-specific T-cell responses that eliminate established tumors and prevent metastatic disease in murine cancer models. We used dogs with HER2/neu(+) appendicular osteosarcoma, a well-recognized spontaneous model for pediatric to determine whether highly attenuated, recombinant monocytogenes expressing chimeric human HER2/neu fusion protein (ADXS31-164) could safely HER2/neu-specific immunity disease.Eighteen underwent limb amputation or salvage surgery...
We generated two humanized interleukin-13 receptor α2 (IL-13Rα2) chimeric antigen receptors (CARs), Hu07BBz and Hu08BBz, that recognized human IL-13Rα2, but not IL-13Rα1. Hu08BBz also canine IL-13Rα2. Both of these CAR T cell constructs demonstrated superior tumor inhibitory effects in a subcutaneous xenograft model glioma compared with EGFRvIII construct used recent phase 1 clinical trial (ClinicalTrials.gov: NCT02209376). The 75% reduction orthotopic growth using low-dose infusion. Using...
Preclinical murine models of chimeric antigen receptor (CAR) T cell therapy are widely applied, but greatly limited by their inability to model the complex human tumor microenvironment and adequately predict safety efficacy in patients. We therefore sought develop a system that would enable us evaluate CAR therapies dogs with spontaneous cancers. developed an expansion methodology yields large numbers canine cells from normal or lymphoma-diseased dogs. mRNA electroporation was utilized...
Different members of the Rel/NF-κB family may play different roles in immunity and inflammation. We report here that c-Rel–deficient mice are resistant to autoimmune encephalomyelitis defective Th1, but not Th2 responses. The Th1 deficiency appears be caused by selective blockade IL-12 production antigen-presenting cells, as well a complete abrogation IFN-γ expression T cells. Interestingly, c-Rel does affect T-bet expression, suggesting act downstream during cell differentiation. Thus,...
Angiosarcomas (AS) are rare in humans, but they a deadly subtype of soft tissue sarcoma. Discovery sequencing AS, especially the visceral form, is hampered by rarity cases. Most diagnostic material exists as archival formalin fixed, paraffin embedded which serves poor source high quality DNA for genome-wide sequencing. We approached this problem through comparative genomics. hypothesized that exome histologically similar tumor, hemangiosarcoma (HSA), occurs approximately 50,000 dogs per...
Abstract The production of IL-12 is required for immunity to many intracellular pathogens. Recent studies have shown that c-Rel, a member the NF-κB family transcription factors, essential LPS-induced IL-12p40 by macrophages. In this study, we demonstrate c-Rel also macrophages in response Corynebacterium parvum, CpG oligodeoxynucleotides, anti-CD40 and low molecular weight hyaluronic acid. However, c-Rel−/− mice infected with Toxoplasma gondii produce comparable amounts wild-type an...
Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendritic cell (DC) vaccine achieving regulatory approval clinical use last year. Manufacturing remains arduous, especially DC vaccines, and prospect of using cell-based in adjuvant setting or combination chemotherapy largely untested. Here, we used comparative oncology approach to test safety potential efficacy tumor RNA-loaded, CD40-activated B cells privately owned dogs presenting non-Hodgkin's...
Multiple rodent and primate preclinical studies have advanced CAR T cells into the clinic. However, no single model accurately reflects challenges of effective therapy in human cancer patients. To evaluate effectiveness next-generation that aim to overcome barriers durable tumor elimination, we developed a system pet dogs with spontaneous cancer. Here report on this results pilot trial using treat canine diffuse large B cell lymphoma (DLBCL). We designed manufactured CD20-targeting,...
Angiosarcoma (AS) is a rare neoplasm with limited treatment options and poor survival rate. Development of effective therapies hindered by the rarity this disease. Dogs spontaneously develop hemangiosarcoma (HSA), common, histologically similar neoplasm. Metastatic disease occurs rapidly despite chemotherapy, most dogs die several months after diagnosis. These features suggest that HSA might provide tractable model to test experimental in clinical trials. We previously reported whole exome...
Abstract The NF-κB family of transcription factors is critical in controlling the expression a wide range immune response genes. However, whether individual members perform specific roles regulating immunity and inflammation remains unclear. Here we investigated requirement for NF-κB1, NF-κB2, c-Rel Th2 cytokine responses, development host protective immunity, regulation intestinal following infection with gut-dwelling helminth parasite Trichuris muris. While mice deficient mounted...
Activated B-cell diffuse large lymphoma (ABC-DLBCL) is an aggressive, poorly chemoresponsive lymphoid malignancy characterized by constitutive canonical NF-κB activity that promotes lymphomagenesis and chemotherapy resistance via overexpression of antiapoptotic target genes. Inhibition the pathway may therefore have therapeutic relevance in ABC-DLBCL. Here, we set out to determine whether dogs with spontaneous DLBCL comparative aberrant inhibition relapsed, resistant DLBCL.Canonical was...
Activated B-Cell (ABC) Diffuse Large Lymphoma (DLBCL) is a common, aggressive and poorly chemoresponsive subtype of DLBCL, characterized by constitutive canonical NF-κB signaling. Inhibition signaling leads to apoptosis ABC-DLBCL cell lines, suggesting targeted disruption this pathway may have therapeutic relevance. The selective IKK inhibitor, NEMO Binding Domain (NBD) peptide effectively blocks activity induces in cells vitro. Here we used comparative approach determine the safety efficacy...
The immune checkpoint inhibitor (ICI) ipilimumab has revolutionized the treatment of patients with different cancer histologies, including melanoma, renal cell carcinoma, and non-small lung carcinoma. However, only a subset shows dramatic clinical responses to treatment. Despite intense biomarker discovery efforts linked trials using CTLA4 blockade, no single prognostic correlate emerged as valid predictor outcome. Client-owned, competent, pet dogs develop spontaneous tumors that exhibit...
Allogeneic invariant natural killer T cells (allo-iNKTs) induce clinical remission in patients with otherwise incurable cancers and COVID-19-related acute respiratory failure. However, their functionality is inconsistent among individuals, they become rapidly undetectable after infusion, raising concerns over rejection limited therapeutic potential. We validate a strategy to promote allo-iNKT persistence dogs, an established large-animal model for novel cellular therapies. identify...
Abstract The ability of many microbial and inflammatory stimuli to activate members the Rel/NF-κB family transcription factors is associated with regulation innate adaptive responses required control infection. Individual play distinct roles during different infectious responses. For example, c-Rel essential for production IL-12 in response LPS, but dispensable Toxoplasma Ag. To assess role immunity intracellular pathogen gondii, wild-type (WT) c-Rel−/− mice were infected immune was...
ABSTRACT The production of interleukin-12 (IL-12) is critical to the development innate and adaptive immune responses required for control intracellular pathogens. Many microbial products signal through Toll-like receptors (TLR) activate NF-κB family members that are IL-12. Recent studies suggest components TLR pathway IL-12 in response parasite Toxoplasma gondii ; however, this independent activation. adaptor molecule TRAF6 involved signaling pathways associates with serine/threonine...
Cyclophosphamide is commonly used with prednisone in the initial treatment of severe idiopathic immune‐mediated hemolytic anemia (IMHA) dogs because retrospective reports suggest its benefit. This randomized controlled prospective clinical trial evaluated whether combined cyclophosphamide and therapy more efficacious than alone IMHA. Eighteen acute, IMHA were randomly assigned to 1 2 groups. The P group received (1–2 mg/kg PO q12h), PC q12h) (50 mg/m q24h for 4 consecutive days a week)...
Abstract Long-term resistance to Toxoplasma gondii is dependent on the development of parasite-specific T cells that produce IFN-γ. CD28 a costimulatory molecule important for optimal activation cells, but CD28−/− mice are resistant T. gondii, demonstrating CD28-independent mechanisms regulate cell responses during toxoplasmosis. The identification B7-related protein 1/inducible costimulator (ICOS) pathway and its ability production IFN-γ suggested this may be involved in required gondii. In...