A5031094885- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Immune cells in cancer
- Pancreatic function and diabetes
- Lung Cancer Research Studies
- T-cell and B-cell Immunology
- Adenosine and Purinergic Signaling
- Neuroendocrine Tumor Research Advances
- Hematopoietic Stem Cell Transplantation
- Nerve injury and regeneration
- Erythrocyte Function and Pathophysiology
- Wound Healing and Treatments
- Chemokine receptors and signaling
- Venous Thromboembolism Diagnosis and Management
- Neuroblastoma Research and Treatments
- Veterinary Oncology Research
- Immune Cell Function and Interaction
- Mesenchymal stem cell research
- Acute Myeloid Leukemia Research
- Viral Infections and Vectors
- Mast cells and histamine
Stanford Cancer Institute
2013-2017
Institute for Stem Cell Biology and Regenerative Medicine
2013-2017
University of Massachusetts Chan Medical School
2017
Cancer Institute (WIA)
2013-2017
Stanford Medicine
2017
Stanford University
2013-2016
California Institute for Regenerative Medicine
2016
Small-cell lung cancer (SCLC) is a highly aggressive subtype of with limited treatment options. CD47 cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found expressed the surface human SCLC cells; therefore, investigated CD47-blocking immunotherapies potential approach for treatment. Disruption interaction SIRPα using anti-CD47 antibodies induced macrophage-mediated...
Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs enable donor HSC engraftment. Previous studies have shown anti-c-Kit monoclonal antibodies deplete from bone marrow niches, allowing engraftment in immunodeficient mice. We show clearance is dependent on...
Significance This is the first in-depth profiling of pancreatic neuroendocrine tumors (PanNETs), to our knowledge, that illuminates fundamental biological processes for this class tumors. Beginning with index case and confirmed additional patient tumors, we showed dependence on paracrine signaling through hepatocyte growth factor (HGF)/receptor tyrosine kinase MET axis. We created a novel cell line derived from well-differentiated PanNET autocrine HGF/MET signaling. also identified...
Most secreted growth factors and cytokines are functionally pleiotropic because their receptors expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of as therapeutics. Stem factor (SCF) is a that acts through c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo it concurrently activates mast cells. We engineered mechanism-based SCF partial agonist impaired...
Cancer immunotherapies hold much promise, but their potential in veterinary settings has not yet been fully appreciated. Canine lymphomas are among the most common tumors of dogs and bear remarkable similarity to human disease. In this study, we examined combination CD47 blockade with anti-CD20 passive immunotherapy for canine lymphoma. The CD47/SIRPα axis is an immune checkpoint that regulates macrophage activation. humans, expressed on cancer cells enables evasion from phagocytosis....
CD47 transduces inhibitory signals through signal-regulatory protein α (SIRPα), a plasma membrane receptor expressed by macrophages. Many cancers upregulate to evade immunosurveillance. We have recently engineered SIRPα variants that potently antagonize for use as anticancer immunotherapeutics. These high-affinity synergize with antineoplastic antibodies lowering the threshold macrophage-mediated destruction of malignant cells.
Abstract CD47 allows cancer cells to evade the immune system by signaling through SIRPa, an inhibitory receptor on macrophages. Therapies that block convert tumor-promoting macrophages a tumoricidal state within tumor microenvironment. We recently developed next-generation antagonists engineering extracellular domain of SIRPa. As single-domain polypeptides, these “high-affinity SIRPa variants” have affinity for human (KD) as low 11.1 pM, approximately 50,000-fold improved over wild-type By...
<p>CV1 does not inhibit proliferation of CLBL-1 cells in vitro.</p>
<p>1E4 antibody binds canine CD20 extracellular domain 2.</p>
<div>Abstract<p>Cancer immunotherapies hold much promise, but their potential in veterinary settings has not yet been fully appreciated. Canine lymphomas are among the most common tumors of dogs and bear remarkable similarity to human disease. In this study, we examined combination CD47 blockade with anti-CD20 passive immunotherapy for canine lymphoma. The CD47/SIRPα axis is an immune checkpoint that regulates macrophage activation. humans, expressed on cancer cells enables...
<p>Combination therapy with CD47-blockade and anti-CD20 antibodies produces in vivo efficacy no overt toxicity.</p>
<p>Recombinant production and evaluation of canine SIRPalpha protein.</p>
<p>Microscopic visualization demonstrates macrophage engulfment of CLBL-1 cells.</p>
<p>CD47 expression on canine cancer samples.</p>
<p>Canine macrophages respond to CD47-blocking therapies in vitro.</p>
<p>1E4 antibody binds canine CD20 extracellular domain 2.</p>
<p>CV1 does not inhibit proliferation of CLBL-1 cells in vitro.</p>