A5042744569- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Multiple Myeloma Research and Treatments
- Bone health and treatments
- Bone Metabolism and Diseases
- Radiopharmaceutical Chemistry and Applications
- Synthesis and Biological Evaluation
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- NF-κB Signaling Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Toxin Mechanisms and Immunotoxins
- Insect Resistance and Genetics
- Calcium signaling and nucleotide metabolism
- Cytokine Signaling Pathways and Interactions
- Thyroid Disorders and Treatments
- Bone health and osteoporosis research
- Pregnancy and Medication Impact
- Advancements in Semiconductor Devices and Circuit Design
- Inflammatory Bowel Disease
- Drug Transport and Resistance Mechanisms
- Medical Imaging Techniques and Applications
- Biosimilars and Bioanalytical Methods
Fred Hutch Cancer Center
2013-2019
Amgen (United States)
2007-2014
University of Washington
2013
IDEX Corporation (United States)
1998
The murine multiple drug resistance (mdr) gene, mdr1a, encodes a 170-kDa transmembrane protein that is expressed in many tissues including intestinal epithelial cells, subset of lymphoid cells and hematopoietic cells. We report mdr1a knockout (mdr1a-/-) mice are susceptible to developing severe, spontaneous inflammation when maintained under specific pathogen-free animal facility conditions. seen mdr1a-/- has pathology similar human inflammatory bowel disease (IBD) defined by dysregulated...
Early clinical results of chimeric antigen receptor (CAR) T cell therapy targeting B maturation (BCMA) for multiple myeloma (MM) appear promising, but relapses associated with residual low-to-negative BCMA-expressing MM cells have been reported, necessitating identification additional targets. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), normally expressed only in the hair follicle, was previously identified as by mRNA marrow aspirates from patients MM,...
Abstract BACKGROUND Metastases to bone are a frequent complication of human prostate cancer and result in the development osteoblastic lesions that include an underlying osteoclastic component. Previous studies rodent models breast have established receptor activator NF‐κB ligand (RANKL) inhibition decreases lesion tumor growth bone. RANK is essential for osteoclast differentiation, activation, survival via its expression on osteoclasts their precursors. has also been observed some cell...
PET targeting a mutated PSMA enabled serial imaging of CAR T cell activity in murine model ALL.
Abstract Anti–B-cell maturation antigen (BCMA) chimeric receptor (CAR) T cells have shown promising clinical responses in patients with relapsed/refractory multiple myeloma. Lenalidomide, an immunomodulatory drug, potentiates cell functionality, drives antimyeloma activity, and alters the suppressive microenvironment; these properties may effectively combine anti-BCMA CAR to enhance function. Using T, we demonstrated that lenalidomide enhances function a concentration-dependent manner....
Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for patients with CD19 + B-cell malignancies. Combination strategies that improve CAR potency, limit tumor environment–mediated immune dysfunction, and directly reduce burden may increase the potential durable clinical benefit of therapy. Lisocabtagene maraleucel (liso-cel) product candidate being tested in relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia. This study assessed vitro vivo...
Abstract Tumor cells induce excessive osteoclastogenesis, mediating pathologic bone resorption and subsequent release of growth factors calcium from matrix, resulting in a “vicious cycle” breakdown tumor proliferation. RANK ligand (RANKL) is an essential mediator osteoclast formation, function, survival. In metastatic prostate cancer models, RANKL inhibition directly prevents osteolysis via blockade osteoclastogenesis indirectly reduces progression skeletal burden by reducing local factor...
Purpose: Alpha‐emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over few cell diameters (50–80 μ m), causing localized, irreparable double‐strand DNA breaks that lead to death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells minimal radiation damage surrounding tissues. Tools are needed visualize and quantify the radioactivity distribution...
The vast majority of patients with plasma cell neoplasms die progressive disease despite high response rates to novel agents. Malignant cells are very radiosensitive, but the potential role radioimmunotherapy (RIT) in management plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 not been explored as a RIT target its uniform expression on malignant cells. In this report, both conventional (directly radiolabeled antibody) streptavidin-biotin pretargeted...
Abstract Receptor activator of NF-κB (RANK) and its ligand (RANKL) are essential for osteoclast formation, function, survival. Osteoprotegerin (OPG) inhibits RANK signaling by sequestering RANKL. This study evaluated the antiosteoclast immunoregulatory effects mouse rRANK-Fc, which, similar to OPG, can bind The effect RANKL inhibition RANK-Fc on function was determined vitamin D3 (1,25(OH)2D3)-induced hypercalcemia. Mice were injected with a single dose 0, 10, 100, 500, or 1000 μg RANK-Fc;...
Abstract #4167 Purpose: RANK and its ligand (RANKL), key factors for bone remodeling metastasis, are crucial the development of mouse mammary gland during pregnancy. Upon treatment with hormone medroxyprogesterone (MPA) a carcinogen (DMBA), transgenic mice overexpressing in via MMTV promoter exhibit higher incidence ductular hyperplasias, intraepithelial neoplasias (MIN), adenocarcinomas than WT mice. This study assessed expression RANKL MMTV-RANK tumor progression this model determined...
In bone metastases, tumor cells interact with the microenvironment to induce osteoclastogenesis, leading destruction and growth factor release. RANK ligand (RANKL) is essential for osteoclast formation, function, survival. Tumor cell-mediated osteolysis thought occur ultimately via induction of RANKL within stroma, inhibition in models breast cancer metastases blocks tumor-induced reduces skeletal burden. addition, skeleton co-opted by functions as a supportive microenvironment. Inhibition...
Abstract Purpose: RANK and its ligand (RANKL), key factors for bone remodeling metastasis, are crucial the development of mouse mammary gland during pregnancy. RANKL functions as a major paracrine effector mitogenic action progesterone in epithelium has role ovarian hormone-dependent expansion regenerative potential stem cells (MaSC). inhibition been shown to reduce tumor formation pulmonary metastases models. Many published expression analyses have performed using immunohistochemistry (IHC)...
Cancer immunotherapy is an exciting area of cancer treatment bolstered by recent success anti-immune checkpoint antibodies in the clinic. Engineered T cells that are programmed to attack tumors via chimeric antigen receptors (CARs) have also shown promise early clinical trials. It speculated, however, PD-1/PD-L1 axis dampens effectiveness CAR therapy certain types. In order improve function transplanted these contexts, we deleted PDCD1 using genome editing system, CRISPR/Cas9. Delivery Cas9...