A5064496505- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- NF-κB Signaling Pathways
- Protein purification and stability
- Veterinary medicine and infectious diseases
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Cancer Cells and Metastasis
- Diabetes and associated disorders
- Animal Nutrition and Physiology
- RNA and protein synthesis mechanisms
- Calcium signaling and nucleotide metabolism
- Growth Hormone and Insulin-like Growth Factors
- Peptidase Inhibition and Analysis
- Trace Elements in Health
- Multiple Myeloma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Antimicrobial Peptides and Activities
- Proteoglycans and glycosaminoglycans research
- Transgenic Plants and Applications
- Protease and Inhibitor Mechanisms
University of Kansas
2019-2021
F-star (United Kingdom)
2015
Biogen (United States)
2003
New Frontier
1993-1997
National Institutes of Health
1991
National Institute of Allergy and Infectious Diseases
1989-1991
London School of Hygiene & Tropical Medicine
1989
The toll-like receptor 7 and 8 (TLR7/8) agonist Resiquimod (R848) has been recognized as a promising immunostimulator for the treatment of cutaneous cancers in multiple clinical trials. However, systemic administration R848 often results strong immune-related toxicities while having limited therapeutic effects to tumor. In present study, prodrug-based nanocarrier delivery system was developed that exhibited high efficiency. conjugated α-tocopherol constitute an R848-Toco prodrug, followed by...
Summary The presentation of extremely low doses antigen to T cells is enhanced by immunoglobulin E (IgE)‐dependent focusing CD23, the low‐affinity receptor for IgE, expressed on activated B cells. CD23 contains a C‐type lectin domain in its extracellular sequence and targeting signal coated pits, required endocytosis, cytoplasmic sequence. non‐covalently associated with major histocompatibility complex class II antigen, human leucocyte HLA‐DR, surface cells, but fate this following...
FS102 is a HER2-specific Fcab (Fc fragment with antigen binding), which binds HER2 high affinity and recognizes an epitope that does not overlap those of trastuzumab or pertuzumab. In tumor cells express levels HER2, caused profound internalization degradation leading to cell apoptosis. The antitumor effect in patient-derived xenografts (PDXs) correlated strongly the amplification status tumors. Superior activity over combination pertuzumab was observed vitro vivo when gene copy number equal...
Modulation of the immune response using immunoglobulin fusion proteins has shown great promise for clinical immunotherapy autoimmune diseases. Alefacept is an protein composed first extracellular domain human LFA-3 fused to hinge, C(H)2 and C(H)3 domains IgG(1). previously been reported inhibit T cell proliferation. Here, we analyzed effects alefacept on lymphocytes in vitro characterized role autologous NK cells its mechanism action. Alefacept, but not a binding mutant inhibited CD3-induced...
In this report, we demonstrate that the T cell activation antigen, recognized by monoclonal antibody H9.2B8, is murine homologue of vitronectin receptor (VNR) and, thereby, provide initial evidence VNR expressed on lymphoid cells. a variety lines, tumors, and Con A-activated splenocytes, but not resting cells, capable binding to extracellular matrix proteins fibronectin, fibrinogen, vitronectin, via tripeptide sequence RGD. There was no novel beta chains pairing with alpha chain, as has been...
Cell-cell and cell-extracellular (ECM) protein interactions are mediated through heterodimers termed integrins. We have demonstrated that dendritic epidermal T cell (DETC) lines adhere to the ECM proteins, fibronectin, fibrinogen, vitronectin but not collagen, laminin, or control proteins. This adhesion was blocked by tetrapeptide RGDS, peptide, RGES. derived a hamster mAb H9.2B8, rat mAb, 8.18E12, from immunizations with DETC lines. The mAbs in combination, individually, specifically...
An Fcab (Fc antigen binding) is a crystallizable fragment of IgG having C-terminal structural loops CH3 domains engineered for binding. Since introduction novel binding sites might impair the immunoglobulin fold, repairing strategies are needed improving biophysical properties promising binders without decreasing affinity to antigen. Here, directed evolution protocol was developed and applied stabilization Her2/neu-binding Fcab. Distinct loop regions parental binder were softly randomized by...
Abstract CD23, the low‐affinity IgE receptor, is up‐regulated on interleukin (IL)‐4‐stimulated B cells and monocytes, with a concomitant increase in release of soluble fragments CD23 (sCD23) into medium by proteolytic processing surface‐bound intact CD23. The effect inhibition production human mouse model vivo was evaluated. to sCD23 from RPMI 8866 (a Epstein‐Barr virus‐transformed cell line) membranes inhibited broad‐spectrum matrix‐metalloprotease inhibitor, batimastat, an IC 50 0.15 μM....
Abstract Antigen‐binding Fc fragments (Fcabs) are a new unique class of immunotherapeutics. They small (50 kD) fully functional antibody alternatives that bind antigen and elicit effector functions such as antibody‐dependent cytotoxicity (ADCC) complement‐dependent cytotoxicity. Since Fcabs carry the natural FcRn binding site antibodies, they have very favorable pharmacokinetics. We showed recently Fcab H10‐03‐6 is high‐affinity binder Her‐2/neu (ErbB2/neu) mediating killing...
CD23 is a multifunctional molecule expressed by cells of lymphoid, myeloid and hematopoietic lineages. As cell surface acts both as low-affinity receptor for IgE (Fc epsilon RII) adhesion molecule. can undergo autoproteolysis to release soluble 37-25-kDa (s-CD23) molecules with range cytokine activities. Here we show causal link between the two apparently disparate functions adhesion. The Epstein-Barr virus-transformed B line RPMI-8866 formed macroscopic clusters solely via CD23. Cell was...
Abstract Regulatory T cells (Treg) are key players of the suppressive tumour microenvironment (TME). Their presence is correlated with a bad prognosis in multiple cancers, while greater ratio effector (Teff) to Treg associated improved outcome. Studies demonstrating high expression CD25 on Tregs but not Teff human tumors have underscored its relevance as target for depletion. However, clinical trials conducted cancer patients existing anti-CD25 (aCD25) antibodies shown contradicting results,...
Abstract Targeting CD38 in multiple myeloma has resulted outstanding responses. is widely expressed on cells and other hematological malignancies. Not much known about its expression solid tumors role the immune system. We have analysed a range of for distribution. To optimally target CD38, we generated novel antibody that depleting CD38-high expressing cells, but also modulatory properties. dissect exploited mRNA libraries, performed histochemistry (IHC) tumor sections, flow cytometry...
ABSTRACT Small molecule agonists of TLR7/8, such as imidazoquinolines, are validated for the treatment cancer and use in vaccine adjuvants. Imidazoquinolines have been extensively modified to understand structure-activity relationship (SAR) at N1- C2-positions resulting clinical drug imiquimod, resiquimod, several other highly potent analogues. However, SAR aryl ring has not fully elucidated literature. This initial study examines C7-substituted imidazoquinolines. These compounds only...