A5075358312- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Monoclonal and Polyclonal Antibodies Research
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- Chronic Myeloid Leukemia Treatments
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Signaling Pathways in Disease
- Toxin Mechanisms and Immunotoxins
- T-cell and B-cell Immunology
- Lysosomal Storage Disorders Research
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Biochemical and Molecular Research
- Vascular Tumors and Angiosarcomas
- melanin and skin pigmentation
- Olfactory and Sensory Function Studies
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Acute Myeloid Leukemia Research
Xencor (United States)
2015-2024
University of California, Los Angeles
2009-2015
APLA Health
2013
University of California, San Francisco
2001-2007
UCSF Helen Diller Family Comprehensive Cancer Center
2005-2007
Indiana University – Purdue University Indianapolis
2005
The RASopathies are a group of genetic syndromes caused by germline mutations in genes that encode components the Ras/mitogen-activated protein kinase (MAPK) pathway. Some these neurofibromatosis type 1, Noonan syndrome, Costello cardio-facio-cutaneous LEOPARD syndrome and Legius syndrome. Their common underlying pathogenetic mechanism brings about significant overlap phenotypic features includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI ocular abnormalities,...
Germ line missense mutations in HRAS and KRAS genes encoding molecules that function up- or downstream of Ras cellular signaling networks cause a group related developmental disorders includes Costello syndrome, Noonan cardiofaciocutaneous syndrome. We performed detailed biochemical functional studies three mutant K-Ras proteins (P34R, D153V, F156L) found individuals with syndrome Mutant demonstrate range gain-of-function effects different cell types, analysis supports the idea intrinsic...
Multiple genetic or molecular alterations are known to be associated with cancer stem cell formation and development. Targeting such alterations, therefore, may lead prevention. By crossing our previously established phosphatase tensin homolog (Pten) - null acute T-lymphoblastic leukemia (T-ALL) model onto the recombination-activating gene 1 −/− background, we show that lack of variable, diversity joining [V(D)J] recombination completely abolishes Tcrα/δ-c-myc translocation T-ALL...
Disease relapse remains the major clinical challenge in treating T-cell acute lymphoblastic leukemia (T-ALL), particularly those with PTEN loss. We hypothesized that leukemia-initiating cells (LIC) are responsible for T-ALL development and treatment relapse. In this study, we used a genetically engineered mouse model of Pten(-/-) defined blast LIC-enriched cell populations to demonstrate LICs therapeutic resistance. Unlike chronic myelogenous leukemia, were actively cycling, distinct...
Ras proteins control a variety of critical cellular processes, and somatic mutations in RAS genes (and other members signaling networks regulated by Ras) are common human malignancies. guanosine triphosphate (GTP)-binding that cycle between active GTP-bound inactive diphosphate (GDP) bound conformations. Cancer-associated typically alter amino acids G12, G13 or Q61. These mutant display impaired GTPase activity resistant to activating (GAPs). We others recently discovered novel germline KRAS...
Costello syndrome is a mental retardation characterized by high birth weight, postnatal growth retardation, coarse face, loose skin, cardiovascular problems, and tumor predisposition. De novo heterozygous missense mutations in HRAS codon 12 13 disturbing the intrinsic GTP hydrolysis cause syndrome. We report patient with typical novel mutation 117 (c.350A>G, p.Lys117Arg) of gene, resulting constitutive activation RAS/MAPK pathway similar to p.Gly12Ser p.Gly12Ala mutations. Recombinant...
Mutations in genes involved Ras signalling cause Noonan syndrome and other disorders characterised by growth disturbances variable neuro-cardio-facio-cutaneous features. We describe two sisters, 46 31 years old, who presented with dysmorphic features, hypotonia, feeding difficulties, retarded psychomotor retardation early life. The patients were initially diagnosed Costello syndrome, autosomal recessive inheritance was assumed. Remarkably, however, we identified a germline HRAS mutation...
Abstract IL15 and IL2 are two similar cytokines that stimulate the proliferation of lymphocytes, their therapeutic potential has been well established in animal models human trials. Both exert cell signaling function through binding to a trimeric complex consisting shared receptors, common gamma chain (γc) IL2Rβ, as an alpha receptor unique each cytokine: IL2Rα or IL15Rα. share biology, with exception greater preference for Tregs due high constitutive expression IL2Rα. functions stabilized...
Abstract An insufficient quantity of functional T cells is a likely factor limiting the clinical activity T-cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate dependent (TDB) antibodies. The activation human peripheral by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted upregulation IL-2/15Rβ (CD122)...
Introduction Interleukin 15 (IL-15) is a potential anticancer agent and numerous engineered IL-15 agonists are currently under clinical investigation. Selective targeting of to specific lymphocytes may enhance therapeutic effects while helping minimize toxicities. Methods We designed built heterodimeric targeted cytokine (TaCk) that consists an anti-programmed cell death 1 receptor antibody (anti-PD-1) IL-15. This “PD1/IL15” selectively delivers signaling expressing PD-1. then investigated...
Abstract Somatostatin receptor 2 (SSTR2) is highly expressed in neuroendocrine tumors (NETs) and small cell lung cancer (SCLC). Treatment options for NETs include somatostatin analogs radionuclides; however, such therapies suffer from short half-life, modest efficacy, toxicities due to inhibition of other SSTRs. Reasoning that a targeted immunotherapy against SSTR2 would provide new therapeutic modality NETs, we designed XmAb18087, humanized affinity-optimized bispecific antibody engages T...
Abstract The IL2Rβ/γc binding human cytokines IL2 and IL15 aid in the activation, proliferation, survival of T NK cells, their therapeutic potential has been well established animal models trials. However, approaches utilizing these have suffered from low tolerability, fast clearance, limited window due to extensive activity on peripheral lymphocytes. Conversely, higher drug concentration prolonged exposure are desirable allow lymphocyte activation proliferation at tumor site, but this can...
Mutations in genes involved Ras signalling cause Noonan syndrome and other disorders characterised by growth disturbances variable neuro-cardio-facio-cutaneous features. We describe two sisters, who presented with dysmorphic features, hypotonia, retarded psychomotor retardation. The patients were initially diagnosed Costello syndrome, an autosomal recessive inheritance was assumed. Remarkably, however, we identified a germline <i>HRAS</i> mutation (G12A) one sister <i>KRAS</i> (F156L) her...
<p>Supplementary figure S2 shows anti-HER-2/CD3 TDB-induced CD122 upregulation</p>
<div>Abstract<p>An insufficient quantity of functional T cells is a likely factor limiting the clinical activity T-cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate dependent (TDB) antibodies. The activation human peripheral by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted upregulation...
<p>Supplementary figure S1 shows the proliferation activity of surrogate mIL-15-Fc</p>