A5030990056- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Advanced Memory and Neural Computing
- CRISPR and Genetic Engineering
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Neural dynamics and brain function
- Nanopore and Nanochannel Transport Studies
- Monoclonal and Polyclonal Antibodies Research
- Extracellular vesicles in disease
- CAR-T cell therapy research
- Neuroscience and Neural Engineering
- Glycosylation and Glycoproteins Research
- Inflammation biomarkers and pathways
- ECG Monitoring and Analysis
- Advanced biosensing and bioanalysis techniques
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Macrophage Migration Inhibitory Factor
- Fuel Cells and Related Materials
- RNA Research and Splicing
- Cancer Immunotherapy and Biomarkers
- CCD and CMOS Imaging Sensors
- Non-Invasive Vital Sign Monitoring
23andMe (United States)
2022-2025
Broad Center
2019
Broad Institute
2019
University of California, San Francisco
2019
Polytechnic University of Turin
2015-2018
Berkeley College
2014
University of California, Berkeley
2014
PD-L1 on the surface of tumor cells binds its receptor PD-1 effector T cells, thereby suppressing their activity. Antibody blockade can activate an anti-tumor immune response leading to durable remissions in a subset cancer patients. Here, we describe alternative mechanism activity involving secretion tumor-derived exosomes. Removal exosomal inhibits growth, even models resistant anti-PD-L1 antibodies. Exosomal from suppresses cell activation draining lymph node. Systemically introduced...
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<p>Supplementary Figure S4</p>
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<p>Supplementary Figure S9</p>
<p>Supplementary Figure S6</p>
<p>Characterization of the binding and blocking activity 23ME-01473</p>
<p>Supplementary Figure S7</p>
Abstract The landscape of cancer treatment has been transformed by immune checkpoint inhibitors; however, the failure to benefit a large number patients with underlined need identify promising targets for more effective interventions. In this study, we leverage 23andMe, Inc.’s large-scale human germline genetic and health database uncover previously unknown role UL16-binding protein 6 (ULBP6), high-affinity NK group 2D (NKG2D) ligand, in its promise as an immuno-oncology therapeutic target....
<p>List of collaborators from 23andMe Research Team</p>
<p>23ME-01473 significantly inhibits the growth of a NSCLC patient-derived xenograft cancer model <i>in vivo.</i><b>A,</b> Cell surface expression ULBP6/2/5 on EpCAM<sup>+</sup> tumor cells from CTG-3470 PDX cell line implanted and grown in NOG mice as measured by flow cytometry. Data three biological replicates are shown. <b>B,</b> Representative IHC images or MICA/B (top) corresponding isotype controls (bottom) resected tumors....
<p>Supplementary Figure S3</p>
<p>Dual FcγRIIIa and NKG2D activation by 23ME-01473, an Fc effector–enhanced anti-ULBP6/2/5 antibody, induces augmented antitumor immunity. <b>A,</b> IFNγ concentration of the supernatants IL-2/IL-15–primed PBMCs cultured with plate-bound antibodies that activate (Fc-WT-anti-lysozyme antibody; X-lys-E+), (Fc-Att-anti-lysozyme antibody fused to ULBP6-02; ULBP6-lys-E−), both receptors ULBP6-lys-E+), or neither receptor X-lys-E−) for 24 hours. Data represent mean ± SD three...
<p>Supplementary Figure S1</p>
<p>mRNA and protein expression of NKG2D ligands in human cancers. <b>A,</b> Heatmap the median mRNA NKG2DLs per cancer type The Cancer Genome Atlas. types are sorted by <i>RAET1L</i> (ULBP6). <b>B,</b> <i>ULBP2</i>, <i>RAET1G</i>, (ULBP5) stromal, immune, malignant cells (<i>N</i> = 5,902) from 18 treatment-naive patients with HNSC. <b>C,</b> Representative IHC images ULBP6/2/5 HNSC LUSC tumors (top)...
<div>Abstract<p>The landscape of cancer treatment has been transformed by immune checkpoint inhibitors; however, the failure to benefit a large number patients with underlined need identify promising targets for more effective interventions. In this study, we leverage 23andMe, Inc.’s large-scale human germline genetic and health database uncover previously unknown role UL16-binding protein 6 (ULBP6), high-affinity NK group 2D (NKG2D) ligand, in its promise as an immuno-oncology...
<p><i>RAET1L</i> (ULBP6) germline genetics. Regional GWAS plots of the three <i>RAET1L</i> variants: rs1543547, rs1555696, and rs61730071, identified in credible set that are significantly associated with (<b>A</b>) alopecia areata (<b>B</b>) basal cell carcinoma. The fourth variant, rs912565, is not either phenotype. <b>C,</b> variants, but showed significant (<i>P</i> < 5 × 10<sup>−8</sup>)...
<p>Supplementary Figure S2</p>
<p>Supplementary Figure S10</p>
<p>ULBP6 may be the most potent NKG2D ligand. <b>A,</b> Equilibrium dissociation constant K<sub>D</sub> for human NKG2DLs binding to as measured by a Biacore surface plasmon resonance assay. Data represent mean ± SD of three technical replicates per condition. ULBP4 is not shown, no was detected. <b>B,</b> IFNγ concentration supernatants IL-2/IL-15–primed PBMCs cocultured with COV644 cells and 0.05 200 nmol/L recombinant sULBP6-02 or sMICA 24 hours,...
<p>Neutralization of soluble ULBP6 by an anti-ULBP6/2/5 antibody promotes NK and CD8<sup>+</sup> T cell activation PBMC-mediated tumor killing. <b>A,</b> Crystal structure 23ME-01473 Fab in complex with human ULBP6-02. The extracellular domain ULBP6-02 is colored orange, glycan moieties from N-glycosylated asparagine are shown as sticks, the coding single-nucleotide polymorphism regions green spheres. surface representation light chain purple heavy dark purple....
<p>Binding affinity of anti-ULBP6/2/5 antibodies to human Fcγ receptors</p>