A5076447196- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cancer Mechanisms and Therapy
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Kruppel-like factors research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Angiogenesis and VEGF in Cancer
- PI3K/AKT/mTOR signaling in cancer
- Radiopharmaceutical Chemistry and Applications
- Cell death mechanisms and regulation
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Nanoparticle-Based Drug Delivery
- Autophagy in Disease and Therapy
- Biosimilars and Bioanalytical Methods
- Protein Tyrosine Phosphatases
- HER2/EGFR in Cancer Research
- Lysosomal Storage Disorders Research
- Ion channel regulation and function
- NF-κB Signaling Pathways
- Signaling Pathways in Disease
- Cancer-related Molecular Pathways
- Phytochemistry and Bioactive Compounds
Xencor (United States)
2016-2024
City Of Hope National Medical Center
2011-2023
Institute of Molecular Medicine
2023
Sanford Burnham Prebys Medical Discovery Institute
2010-2012
City of Hope
2008-2011
Beckman Research Institute
2009-2011
Virginia Commonwealth University
2010-2011
AstraZeneca (United States)
2011
Bristol-Myers Squibb (United States)
2008
Cedars-Sinai Medical Center
2004-2007
Limited options are available for treating patients with advanced prostate cancer (PC). Melanoma differentiation associated gene-7/interleukin-24 ( mda -7/IL-24), an IL-10 family cytokine, exhibits pleiotropic anticancer activities without adversely affecting normal cells. We previously demonstrated that suppression of the prosurvival Bcl-2 member, myeloid cell leukemia-1 (Mcl-1), is required -7/IL-24–mediated apoptosis carcinomas. Here we demonstrate pharmacological inhibition Mcl-1...
Abstract Glioblastoma is the most common type of primary brain tumor and rapidly progressive with few treatment options. Here, we report that sorafenib (≤10 μmol/L) inhibited cell proliferation induced apoptosis in two established lines (U87 U251) cultures (PBT015 PBT022) from human glioblastomas. The effects on these cells were associated inhibiting phosphorylated signal transducers activators transcription 3 (STAT3; Tyr705). Expression a constitutively activated STAT3 mutant partially...
STAT3 has important functions in both tumor cells and the microenvironment to facilitate cancer progression. The STAT regulatory kinase Janus-activated (JAK) been strongly implicated promoting oncogenesis of various solid tumors, including use JAK inhibitors such as AZD1480. However, direct evidence that drives function pathogenesis at level is yet be established clearly. In this study, we show AZD1480 inhibits tumor-associated myeloid cells, reducing their number inhibiting metastasis....
Abstract Medulloblastomas are the most frequent malignant brain tumors in children. Sunitinib is an oral multitargeted tyrosine kinase inhibitor used clinical trials as antiangiogenic agent for cancer therapy. In this report, we show that sunitinib induced apoptosis and inhibited cell proliferation of both a short-term primary culture (VC312) established line (Daoy) human medulloblastomas. treatment resulted activation caspase-3 cleavage poly(ADP-ribose) polymerase upregulation proapoptotic...
Autophagy is a lysosomal degradation pathway that converts macromolecules into substrates for energy production during nutrient-scarce conditions such as those encountered in tumor microenvironments. Constitutive mitochondrial uptake of endoplasmic reticulum (ER) Ca 2+ mediated by inositol triphosphate receptors (IP 3 Rs) maintains cellular bioenergetics, thus suppressing autophagy. We show the ER membrane protein Bax inhibitor-1 (BI-1) promotes autophagy an IP R-dependent manner. By...
Medulloblastomas are the most frequent malignant brain tumors in children. Sorafenib (Nexavar, BAY43-9006), a multikinase inhibitor, blocks cell proliferation and induces apoptosis variety of tumor cells. inhibited induced two established lines (Daoy D283) primary culture (VC312) human medulloblastomas. In addition, sorafenib phosphorylation signal transducer activator transcription 3 (STAT3) both The inhibition phosphorylated STAT3 (Tyr(705)) occurs dose- time-dependent manner. contrast,...
Stat3 is a latent transcription factor that promotes cell survival and proliferation often constitutively active in multiple cancers. Inhibition of signaling pathways suppresses signals leads to apoptosis cancer cells, suggesting direct inhibition function viable therapeutic approach. Herein, we identify small molecule, C48, as selective Stat3-family member inhibitor. To determine its mechanism action, used site-directed mutagenesis biochemical techniques show C48 alkylates Cys468 Stat3,...
Abstract Adenovirus (Ad)‐based gene therapy represents a potentially viable strategy for treating colorectal cancer. The infectivity of serotype 5 adenovirus (Ad.5), routinely used as transgene delivery vector, is dependent on Coxsackie‐adenovirus receptors (CAR). CAR expression downregulated in many cancers thus preventing optimum therapeutic efficiency Ad.5‐based therapies. To overcome the low problem, chimerism approach was to generate recombinant Ad (Ad.5/3) that capable infecting cancer...
<p>XmAb808 enhances T-cell recall responses to endogenous pMHC ligands. <b>A</b> (top graph), Levels of HLA-A2 on A431-β2M-null cells expressing a fusion protein β2M and HLA-A*0201 fused CMV pp65 NLV peptide (A431-NLV, dashed black) or melanoma G209 (A431-G209, solid gray) were compared with the signal from unstained (solid black). (two bottom graphs), PBMCs two unique CMV–seropositive donors stained HLA-A*0201-CMV-pp65 (NLV) tetramers; percentage tetramer+...
<p>XmAb808 enhances the activity of an EpCAM×CD3 TCE <i>in vitro</i>. <b>A</b> and <b>B,</b> 22Rv1-NLR cells were cocultured with T at E:T ratio 10:1 treated a dose titration (closed symbols) or without (open 1 μg/mL XmAb808. <b>A,</b> After 24 hours, IL2 IFNγ secretion was measured, CD25<sup>+</sup> Bcl-xL<sup>+</sup> counted. cell counts are presented as percentage total CD4<sup>+</sup>...
<p>An XmAb808 analogue enhances antitumor activity of an EpCAM×CD3 TCE in human PBMC-engrafted mice. NSG-MHC I/II DKO mice were intradermally inoculated with HPAF-II cells. After 2 weeks, palpable tumors formed, and then engrafted PBMCs together 5 mg/kg alone or combination 1 B7-H3×Null XmAb808<sup>s</sup> weekly. <b>A,</b> Tumor volumes are shown over time as mean ± SEM <i>n</i> = 8–10 mice/group. <b>B,</b> individual at the end study....
<p>XmAb808 binds avidly to B7-H3 on target cells costimulate T cells. <b>A,</b> Binding of XmAb808 or its analogue containing a single B7-H3–binding domain (mono–B7-H3×CD28) with varying densities (left axis) and binding human (right are plotted as mean fluorescence intensity (MFI). HEK293 express approximately 200,000 antigens; A431, 196,000; 22Rv1, 86,000; LOX-IMVI do not B7-H3. Because mono–B7-H3×CD28 has lower molecular weight than (145 vs. 192 kDa), the concentrations...
<p>XmAb808 combines with an anti–PD-1 antibody to suppress tumor growth in human PBMC-engrafted mice. NSG-MHC I/II DKO mice were intradermally inoculated MDA-MB-231-pp65 cells. After 18 days, palpable tumors formed, and engrafted PBMCs together 3 mg/kg of XmAb808 and/or weekly. <b>A,</b> Tumor volumes are shown over time as mean ± SEM 10 mice/group. <b>B,</b> individual at the end study. Each horizontal line represents values. <b>C</b>...
<p>Supplementary Figure S1: XmAb808 Combines With TCEs to Promote IL2 secretion in Naive, Central Memory, Effector and TEMRA T Cells.</p>
<p>Supplementary Figure 2. XmAb808 Combines With a B7-H3×CD3 TCE to Stimulate IL2 and IFNγ Release From Chronically Stimulated, Exhausted T Cells.</p>
<div>Abstract<p>T-cell activation is a multistep process requiring T-cell receptor engagement by peptide–MHC complexes (Signal 1) coupled with CD28-mediated costimulation 2). Tumors typically lack expression of CD28 ligands, so tumor-specific Signal 1 (e.g., neoepitope presentation) without may be ineffective or even induce anergy. We designed the bispecific antibody XmAb808 to co-engage tumor-associated antigen B7-H3 promote within tumor microenvironment. was measured its...
<p>CD28 costimulation drives activation and survival of T cells, leading to IL2-dependent killing cancer cells. Target cells were cocultured with human (E:T = 1:1) treated XmAb808. <b>A,</b> After 24 hours, IL2 (closed symbols) IFNγ (open measured in culture supernatants. <b>B,</b> The percentages CD4<sup>+</sup> or CD8<sup>+</sup> that CD25<sup>+</sup> Bcl-xL<sup>+</sup> from cocultures 22Rv1-αCD3 following hours...
Abstract T-cell activation is a multistep process requiring receptor engagement by peptide-major histocompatibility complexes (Signal 1) coupled with CD28-mediated costimulation 2). Tumors typically lack expression of CD28 ligands, so tumor-specific Signal 1 (e.g., neoepitope presentation) without may be ineffective or even induce anergy. We designed the bispecific antibody XmAb808 to co-engage tumor-associated antigen B7-H3 promote within tumor microenvironment. was measured its ability...
Abstract Combination checkpoint blockade promotes productive anti-tumor clinical responses often associated with an increase in immune-related adverse events. We developed optimized bispecific antibody candidates that simultaneously engage PD1 and CTLA4 (XmAb20717), LAG3 (XmAb22841), ICOS (XmAb23104), preferentially bind to cells co-expressing the targeted receptors. Because tumor infiltrating lymphocytes (TILs) typically express multiple immune checkpoints costimulatory receptors, we...