A5048109671- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Galectins and Cancer Biology
- Hematopoietic Stem Cell Transplantation
- Lipid Membrane Structure and Behavior
- Cancer, Hypoxia, and Metabolism
- Mesenchymal stem cell research
- Extracellular vesicles in disease
- Acute Lymphoblastic Leukemia research
- Lanthanide and Transition Metal Complexes
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatic function and diabetes
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Glycosylation and Glycoproteins Research
- Lymphoma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
University of Wisconsin–Madison
2013-2021
University of Wisconsin Carbone Cancer Center
2014-2018
University of California, Davis
2013-2015
University of Nevada, Reno
2009-2014
California State University, Sacramento
2013
University of California System
2013
Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, majority of preclinical mouse tumor models assessing potential efficacy toxicities therapeutics use young mice. We assessed impact age on responses systemic immune stimulation. In contrast mice, cancer IT regimens or LPS given aged mice resulted rapid lethal affecting multiple organs correlating with heightened proinflammatory cytokines systemically within parenchymal...
Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration aged, but not young, mice resulted induction of rapid and lethal cytokine storm. found aging was accompanied by increases visceral fat similar to seen young obese (ob/ob or diet-induced [DIO]) mice. Yet, the effects obesity on inflammatory responses immunotherapeutics are well defined. determine adiposity IT tolerance aged compared with Both ob/ob- DIO-generated...
Abstract Inhibitors of adaptive immune checkpoints have shown promise as cancer treatments. CD47 is an innate checkpoint receptor broadly expressed on normal tissues and overexpressed many tumors. Binding tumor to signal regulatory protein alpha (SIRPα) macrophages dendritic cells triggers a “don't eat me” that inhibits phagocytosis enabling escape surveillance. Blocking CD47/SIRPα interaction promotes reducing burden in numerous xenograft syngeneic animal models. We developed...
Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat graft-versus-host disease (GVHD) shown mixed results. Macrophages (MØs) are important regulators of immunity can promote regeneration remodeling. We previously that educate MØs toward a unique anti-inflammatory immunophenotype (MSC-educated [MEMs]); however, their implications for in vivo models inflammation not been studied yet. now show comparison with MØs,...
The availability of clinical-grade cytokines and artificial antigen-presenting cells has accelerated interest in using natural killer (NK) as adoptive cellular therapy (ACT) for cancer. One the technological shortcomings translating therapies from animal models to clinical application is inability effectively non-invasively track these after infusion patients. We have optimized nonradioactive isotope fluorine-19 (19F) a means label NK preclinical magnetic resonance imaging (MRI). Human were...
Because of increasing interest in the removal immunosuppressive pathways cancer, combination IL-2 with Abs to neutralize TGF-β, a potent cytokine, was assessed. Combination immunotherapy resulted significantly greater antitumor effects. These were correlated significant increases numbers and functionality NK cells, cell progenitors, activated CD8 T resulting observed also accompanied by lesser toxicities than therapy alone. Additionally, we dual competition between cells such that, after...
The primary tumor represents a potential source of antigens for priming immune responses disseminated disease. Current means debulking tumors involves the use cytoreductive conditioning that impairs cells or removal by surgery. We hypothesized activation system could occur through localized release and induction death due to physical disruption architecture destruction in situ. This was accomplished intratumor injection magneto-rheological fluid (MRF) consisting iron microparticles, Balb/c...
Abstract Background: Based on its single-agent clinical activity and excellent safety profile, OR502 has best-in-class properties. Preclinically, reverses prevents myeloid cell-mediated immune suppression restores T cell functions with superior than other antibodies targeting LILRB2. binds to a distinct epitope of LILRB2, blocks more broadly LILRB2 binding ligands. In addition, co-engages activating FcγR cells. Here we report pharmacokinetic (PK) receptor occupancy (RO) data from phase 1...
Abstract Background: OR502 is a best-in-class LILRB2 antagonist antibody with strong pre-clinical evidence of efficacy, now confirmed by durable clinical monotherapy responses. prevents LILRB2-mediated immunosuppression myeloid cells blocking LILBR2 binding to human leukocyte antigen-class I proteins. It potentiates Th1-like innate immune responses, rescues T-cells from M2c macrophage-mediated suppression and restores T-cell proliferation effector functions. reduces immunosuppressive...
2524 Background: OR502 is a humanized IgG1 antibody that targets LILRB2, blocking its binding to HLA ligands A, B and G. prevents reverses myeloid cell-mediated immune suppression rescues T cell effector functions. Preclinical data demonstrate best-in-class properties. We report on the completed monotherapy combination dose escalation cohorts from ongoing, first-in-human, phase 1-2 study of this novel antibody. Methods: Patients had progressive, histologically confirmed,...
TPS2669 Background: LILRB2 is an inhibitory receptor expressed on myeloid cells, including tumor-associated macrophages, which binds to HLA-class I proteins and associated with poor outcomes in multiple cancers. OR502 a humanized immunoglobulin G1 antibody that blocks binding proteins. Preclinically, has demonstrated best-in-class reversal prevention of cell-mediated immune suppression restoration T cell functions. Using tackle immunosuppression improve responses the tumor microenvironment...
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to elimination of tumor cells. Clinical efforts also illuminated limitations, however, potential cell antigenic drift neoantigen formation, which promote escape recurrence, as well rapid onset exhaustion vivo. These findings suggest antigen unrestricted such Natural Killer (NK) may...
Cancer immunotherapy holds great promise, yet its efficacy and applicability can be hampered by the rise of systemic toxicities. We have recently shown that lethal side effects cancer are markedly exacerbated with aging. Blocking tumor necrosis factor α or macrophages alleviate toxicity while preserving antineoplastic effects.
Targeting the JAK/STAT and BCL2 pathways in patients with relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) may provide an alternative approach to achieve clinical remissions. Ruxolitinib venetoclax show a dose-dependent effect on T-ALL individually, but combination treatment reduces survival proliferation of vitro. Using xenograft model, fails improve survival, death from hind limb paralysis. Despite on-target inhibition by drugs, histopathology demonstrates increased leukemic...
Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. It has been previously reported that lung GVHD severity directly correlates with the expansion donor Th17 cells in absence IFN-γ. However, consequence Th17-associated presence IFN-γ not well characterized. In current study, T from receptor knockout (IFN-γR(-/-)) mice, capable producing but unable to signal response IFN-γ, have used elucidate further role GVHD. We found transfer either...