A5091683793- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Immune Response and Inflammation
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Radiopharmaceutical Chemistry and Applications
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Renal Diseases and Glomerulopathies
- interferon and immune responses
- Cytomegalovirus and herpesvirus research
- Tryptophan and brain disorders
- Complement system in diseases
- HIV Research and Treatment
- Lung Cancer Treatments and Mutations
- PARP inhibition in cancer therapy
- Genomics, phytochemicals, and oxidative stress
- Pharmacological Effects of Natural Compounds
- Silicon Carbide Semiconductor Technologies
- Bioactive Compounds and Antitumor Agents
Protein Express (United States)
2022-2025
The Wistar Institute
2013-2024
Moffitt Cancer Center
2010-2023
Hospital for Sick Children
2013-2016
National Institutes of Health
2014-2016
Pfizer (United Kingdom)
2016
Gilead Sciences (United States)
2016
National Cancer Institute
2014
SickKids Foundation
2013
University of Toronto
2013
T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous CAR patients with advanced CD19(+) B-cell malignancies.
Myeloid-derived suppressor cells (MDSCs) are a major component of the immune-suppressive network described in cancer and many other pathological conditions. We demonstrate that although MDSCs from peripheral lymphoid organs tumor site share similar phenotype morphology, these display profound functional differences. MDSC suppressed antigen-specific CD8+ T but failed to inhibit nonspecific cell function. In sharp contrast, both activity. The microenvironment caused rapid dramatic...
Adoptive cell transfer, the infusion of large numbers activated autologous lymphocytes, can mediate objective tumor regression in a majority patients with metastatic melanoma (52 93; 56%). Addition and intensification total body irradiation (TBI) to preparative lymphodepleting chemotherapy regimen sequential trials improved partial complete response (CR) rates. Here, we evaluated importance adding TBI adoptive transfer tumor-infiltrating lymphocytes (TIL) randomized fashion.A 101 melanoma,...
A deletion variant of epidermal growth factor receptor (EGFRvIII) is a known driver mutation in subset primary and secondary glioblastoma multiforme. Adoptive transfer genetically modified chimeric antigen (CAR) lymphocytes has demonstrated efficacy hematologic malignancies but still early development for solid cancers. The surface expression the truncated extracellular ligand domain created by EGFRvIII makes it an attractive target CAR-based cancer treatment. Patients with recurrent...
Myeloid-derived suppressor cells (MDSC) are one of the major factors responsible for immune suppression in cancer. Therefore, it would be important to identify effective therapeutic means modulate these cells.We evaluated effect synthetic triterpenoid C-28 methyl ester 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid (CDDO-Me; bardoxolone methyl) MC38 colon carcinoma, Lewis lung and EL-4 thymoma mouse tumor models, as well blood samples from patients with renal cell cancer soft tissue sarcoma....
Myeloid-derived suppressor cells (MDSC) are widely implicated in immune suppression associated with tumor progression and chronic inflammation. However, very little is known about their possible role development. Here, we evaluated the of MDSC two experimental models lung cancer: inflammation-associated cancer caused by chemical carcinogen urethane combination exposure to cigarette smoke; a transgenic CC10Tg model not Exposure mice smoke alone resulted significant accumulation various organs...
Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding viral spike receptor domain (RBD) host angiotensin-converting enzyme II (ACE2) may be effective inhibitors cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 assay identified (-)-hopeaphenol, resveratrol tetramer, in...
Janus kinase 2 (JAK2) is involved in the downstream activation of signal transducer and activator transcription 3 (STAT3) STAT5 responsible for transducing signals several proinflammatory cytokines pathogenesis rheumatoid arthritis (RA), including interleukin (IL)-6, interferon γ (IFNγ) IL-12. In this paper, we describe efficacy profile CEP-33779, a highly selective, orally active, small-molecule inhibitor JAK2 evaluated two mouse models RA.Collagen antibody-induced (CAIA) collagen type II...
Accumulating evidence suggests that autoreactive plasma cells play an important role in systemic lupus erythematosus (SLE). In addition, several proinflammatory cytokines promote B cell maturation and autoantibody production. Hence, therapeutic targeting of such cytokine pathways using a selective JAK2 inhibitor, CEP-33779 (JAK2 enzyme IC(50) = 1.3 nM; JAK3 IC(50)/JAK2 65-fold), was tested two mouse models SLE. Age-matched, MRL/lpr or BWF1 mice with established SLE nephritis, respectively,...
Natural killer (NK) cells can efficiently mediate antibody-dependent cellular cytotoxicity (ADCC) of antibody coated target via the low-affinity Fc-receptor, CD16, but cannot retain antibodies over time. To increase retention and facilitate targeted ADCC, we genetically modified human NK with high-affinity Fc receptor, CD64, so that could preload them HIV-specific broadly neutralizing (BNAbs) enhance their capacity to HIV-infected ADCC. Purified from peripheral blood control donors or...
Constitutively activated STAT3 and STAT5 are expressed in a wide variety of human malignancies including solid hematopoietic cancers often correlate with poor prognosis resistance to multiple therapies. Given the well established role tumorigenesis, inhibition Janus-activated kinase 2 (JAK2) activity might represent an attractive therapeutic approach. Using mouse model colitis-induced colorectal cancer, we show that novel, orally active, selective JAK2 inhibitor, CEP-33779, induced...
Purpose: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition immunogenic somatic mutations expressed by cancer. There are limited data regarding immunogenicity breast We sought to identify nonsynonymous a patient triple-negative cancer (TNBC) and isolate mutation-reactive TILs for possible use adoptive cell transfer.Experimental Design: A TNBC metastasis was resected TIL...
Systemic Lupus Erythematosus (SLE) is a debilitating and often fatal autoimmune disease that involves multiple organ systems. It can develop for years before being diagnosed. Current treatments SLE usually involve the use of cytotoxic or immunosuppressive agents lead to infection cancer. The design appropriate models assays will determine efficiency speed with which an investigator test new chemical entity (NCE) expect results move drug discovery program forward. This unit describes series...
The use of mouse models to study human disease provides useful data that can provide support for research projects or an existing drug discovery program. How well a model recapitulates the condition and ease reproducibility collected will determine how much confidence scientist place on results obtained. Designing new treatments rheumatic diseases, such as rheumatoid arthritis (RA), requires complex immunocompetent depend intricate cytokine networks. Using local cytokines, signal...