A5056285194- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Chronic Lymphocytic Leukemia Research
- Advanced Biosensing Techniques and Applications
- Synthesis and Biological Evaluation
- T-cell and B-cell Immunology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Toxin Mechanisms and Immunotoxins
- Radiopharmaceutical Chemistry and Applications
- Lymphoma Diagnosis and Treatment
- Blood Coagulation and Thrombosis Mechanisms
- Polydiacetylene-based materials and applications
- Cancer Research and Treatments
- Fibroblast Growth Factor Research
- Porphyrin and Phthalocyanine Chemistry
- Estrogen and related hormone effects
- Supramolecular Self-Assembly in Materials
- SARS-CoV-2 and COVID-19 Research
- Biosimilars and Bioanalytical Methods
- Neuroendocrine Tumor Research Advances
- Sex and Gender in Healthcare
Xencor (United States)
2015-2024
California Library Association
2013
KLA (United States)
2010
Pfizer (United States)
2006
Florida State University
2001-2005
Mayo Clinic
2001
University of Nevada, Reno
2000
Abstract CD19 is a pan B-cell surface receptor expressed from pro–B-cell development until its down-regulation during terminal differentiation into plasma cells. represents an attractive immunotherapy target for cancers of lymphoid origin due to high expression levels on the vast majority non–Hodgkin's lymphomas and some leukemias. A humanized anti-CD19 antibody with engineered Fc domain (XmAb5574) was generated increase binding Fcγ receptors immune cells thus Fc-mediated effector functions....
Despite advances in the treatment of multiple myeloma, new therapies are needed to induce more profound clinical responses. T-cell-redirected lysis triggered by bispecific antibodies recruiting T cells cancer is a clinically validated mechanism action against hematologic malignancies and CD38 tumor-associated antigen with near-universal expression myeloma. Thus, an anti-CD38/CD3 T-cell-recruiting antibody has potential be effective therapeutic for myeloma.Anti-CD38/CD3 XmAb different...
The human kallikreins are a large multigene family of closely related serine-type proteases. In this regard, they similar to the kallikrein families characterized in mice and rats. There is much more extensive body knowledge regarding function mouse rat comparison with kallikreins. Human 6 has been proposed as homologue myelencephalon-specific protease, an arginine-specific degradative-type protease abundantly expressed central nervous system implicated demyelinating disease. We present...
Kallikrein 6 (K6, MSP) is a newly identified member of the family serine proteases that preferentially expressed in adult central nervous system (CNS). We have previously demonstrated K6 abundantly by inflammatory cells at sites CNS inflammation and demyelination animal models multiple sclerosis (MS) human MS lesions. To test hypothesis this novel enzyme mediator pathogenesis disease, we evaluated whether autonomously generated antibodies alter clinicopathological course disease murine...
Bispecific monoclonal antibodies can bind two protein targets simultaneously and enable therapeutic modalities inaccessible by traditional mAbs. formats containing a heterodimeric Fc region are of particular interest, as empowers both bispecificity altered valencies while retaining the developability druggability antibody. We present robust platform, called XmAb® bispecific engineered for efficient development fusions multiple formats. First, we engineer purification solution proteins using...
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack therapeutics, has paralyzed the globe. Although significant effort been invested in identifying antibodies that block infection, ability to target infected cells through Fc interactions may be vital eliminate virus. To explore role activity SARS-CoV-2 immunity, functional potential cross-SARS-reactive antibody, CR3022, was assessed. CR3022 able broadly drive antibody effector functions,...
The tumor-associated antigen STEAP1 is a potential therapeutic target that expressed in most prostate tumors and at increased levels metastatic castration-resistant cancer (mCRPC). We developed STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), designed to redirect T cells kill express STEAP1. mediates potent cell-dependent cytotoxicity of cell lines vitro promotes tumor regression xenograft syngeneic mouse models vivo. avidity-driven activity...
Myelencephalon-specific protease (MSP), first identified in the rat and now known to have a human homologue (human kallikrein 6), is preferentially expressed central nervous system (CNS), compared with nonneural tissues. MSP has been postulated trypsin-like activity, upregulated response glutamate receptor-mediated excitotoxic injury CNS, downregulated brain of Alzheimer's patients. The preferential expression this enzyme by oligodendrocytes CNS white matter points role myelin homeostasis....
Abstract Human kallikreins are serine proteases that comprise a recently identified large and closely related 15‐member family. The include both regulatory‐ degradative‐type proteases, impacting variety of physiological processes including regulation blood pressure, neuronal health, the inflammatory response. While function majority remains to be elucidated, two members useful biomarkers for prostate cancer several others potentially breast cancer, Alzheimer's, Parkinson's disease. tissue...
HM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs). In this study, we investigated in vitro and vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb Fc-domain engineered to significantly enhance FcγR binding associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative the IgG1 analog against both MM cell lines primary...
XmAb24306 is a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein currently under clinical investigation as an immunotherapeutic agent for cancer treatment. contains mutations in IL-15 that attenuate its affinity to the heterodimeric βγ (IL-15R). We observe substantially prolonged pharmacokinetics (PK) (half-life ∼ 2.5 4.5 days) single- and repeat-dose cynomolgus monkey (cyno) studies compared wild-type 1 hour), leading increased exposure enhanced durable...
Abstract A 1.10‐Å atomic resolution X‐ray structure of human fibroblast growth factor 1 (FGF‐1), a member the β‐trefoil superfold, has been determined. The is one 10 fundamental protein superfolds and only superfold to exhibit 3‐fold structural symmetry (comprising 3 “trefoil” units). quality diffraction data permits unambiguous assignment Asn, Gln, His rotamers, Pro ring pucker, as well refinement anisotropic displacement parameters (ADPs). FGF‐1 exhibits numerous core‐packing defects,...
The CTLA4-Ig fusion proteins abatacept and belatacept are clinically proven immunosuppressants used for rheumatoid arthritis renal transplant, respectively. Given that both biologics typically administered chronically by infusion, a need exists next-generation with more convenient dosing. We structure-based protein engineering to optimize the affinity of existing therapeutics ligands CD80 CD86, neonatal Fc receptor, FcRn. From rationally designed library, we identified four substitutions...
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 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 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)...