A5084768396- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Bioinformatics and Genomic Networks
- Synthesis and Reactions of Organic Compounds
- Psoriasis: Treatment and Pathogenesis
- Bioactive Compounds and Antitumor Agents
- Gene expression and cancer classification
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Chronic Lymphocytic Leukemia Research
- Advanced Breast Cancer Therapies
- Renin-Angiotensin System Studies
- Multiple Myeloma Research and Treatments
Compugen (Israel)
2013-2024
Johns Hopkins University
2021
Society for Immunotherapy of Cancer
2014
Hebrew University of Jerusalem
2006-2011
Universidade Federal de Minas Gerais
2010
Sheba Medical Center
2001-2002
Tel Aviv University
2001
Background Current therapy for osteosarcoma pulmonary metastases (PMs) is ineffective. The mechanisms that prevent successful immunotherapy in are incompletely understood. We investigated the tumor microenvironment of metastatic with goal harnessing immune system as a therapeutic strategy. Methods 66 tissue specimens were analyzed by immunohistochemistry (IHC) and markers digitally quantified. Tumor-infiltrating lymphocytes (TILs) from 25 profiled functional cytometry. Comparative...
LAP2beta is an integral membrane protein of the nuclear envelope involved in chromatin and architecture. Using yeast two-hybrid system, we have cloned a novel LAP2beta-binding protein, mGCL, which contains BTB/POZ domain mouse homologue Drosophila germ-cell-less (GCL) protein. In embryos, GCL was shown to be essential for germ cell formation localized envelope. Here, show that, mammalian cells, co-localized with Nuclear fractionation studies reveal that mGCL acts as matrix component not...
Mas stimulation with angiotensin (Ang)-(1-7) produces cardioprotective effects and vasorelaxation. Using a computational discovery platform for predicting novel naturally occurring peptides that may activate G protein-coupled receptors, we discovered agonist peptide, CGEN-856S. An endothelium- NO-dependent vasodilating effect was observed CGEN-856S in thoracic aorta rings of rats (maximal value the relaxant effect: 39.99+/-5.034%), which similar to produced by Ang-(1-7) (10(-10) 10(-6)...
Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue (STS), rhabdomyosarcomas and undifferentiated pleomorphic (UPS), differing genetic underpinnings responses to understand mechanisms that lead response.Utilizing fresh formalin-fixed, paraffin-embedded tissue from patients diagnosed UPS rhabdomyosarcomas, dissected TME by using IHC, flow cytometry, comparative...
Activation of the formyl-peptide receptor-like (FPRL) 1 pathway has recently gained high recognition for its significance in therapy inflammatory diseases. Agonism at FPRL1 affords a beneficial effect animal models acute conditions, as well chronic TIPMFVPESTSKLQKFTSWFM-amide (CGEN-855A) is novel 21-amino acid peptide agonist and also activates FPRL2. CGEN-855A was discovered using computational platform designed to predict G protein-coupled receptor agonists cleaved from secreted proteins...
CGEN-856S is a novel Mas agonist. Herein, we examined the effects of this peptide on isoproterenol (ISO)-induced cardiac remodeling and myocardial infarction (MI) injury. We also sought to determine whether activates underlying mechanisms related receptor activation. Heart hypertrophy fibrosis were induced by ISO (2 mg·kg−1·day−1) in Wistar rats. After 7-day treatment period with (90 µg·kg−1·day−1) or vehicle, cardiomyocyte diameter was evaluated left ventricular sections stained hematoxylin...
Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- NK-cell activity stimulates IFNγ production. The of naturally blocked by high-affinity endogenous binding protein (IL18BP). IL18BP induced in the tumor microenvironment (TME) response upregulation negative feedback mechanism. In this study, we found that upregulated TME compared with...
Prostate cancer is a common and heterogeneous disease, where androgen receptor (AR) signaling plays pivotal role in development progression. The initial treatment for advanced prostate suppression of signaling. Later on, essentially all patients develop an independent stage which does not respond to anti hormonal treatment. Thus, alternative strategies targeting novel molecular mechanisms are required. beta-TrCP E3 ligase that targets various substrates essential many aspects...
Abstract The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies human diseases. We identified Ig-like domain–containing receptor (ILDR)2 as a with robust T cell inhibitory activity, expressed in immune cells immune-privileged inflamed tissues. A fusion protein, consisting ILDR2 extracellular domain an Fc fragment, that binds to putative counterpart on activated showed beneficial effect collagen-induced...
β-TrCP, the substrate recognition subunit of a Skp1–Cul1–F-box (SCF) ubiquitin ligase, is ubiquitously expressed from two distinct paralogs, targeting many regulatory proteins for proteasomal degradation. We generated inducible β-TrCP hypomorphic mice and found that they are surprisingly healthy, yet have severe testicular defect. show paralogs nonredundant role in spermatogenesis. The defect tightly associated with cell adhesion failure within seminiferous tubules fully reversible upon...
Abstract Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as subgroup of possess strong proliferative capacity and can expand differentiate following interactions dendritic (DCs). In this study, we explored the pattern expression recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) its ligand, ligand...
### O1 Combinatorial CD8+ and PD-L1+ cell densities correlate with response improved survival in non-small lung cancer (NSCLC) patients treated durvalumab #### Sonja Althammer1, Keith Steele2, Marlon Rebelatto2, Tze Heng Tan1, Tobias Wiestler1, Guenter Schmidt1, Brandon Higgs2, Xia
Abstract The immunoglobulin-like domain containing receptor 2 (ILDR2), a type I transmembrane protein belonging to the B7 family of immunomodulatory receptors, has been described induce an immunosuppressive effect on T-cell responses. Besides its expression in several nonlymphoid tissue types, we found that ILDR2 was also expressed fibroblastic reticular cells (FRC) stromal part lymph node. These immunoregulatory were located zone and essential for recruitment naïve T activated dendritic...
3597 Background: There is a high unmet need for the treatment of patients [pts] with metastatic microsatellite stable colorectal cancer [MSS-CRC]. We reported encouraging preliminary antitumor activity combination COM701 + nivolumab in MSS-CRC and liver metastases [12/22(77%)], [ORR 2/17 (12%); disease control rate [DCR] 5/17 (29%)] 1 . novel, 1st-in-class immune checkpoint inhibitor [ICI] that binds to PVRIG, DNAM-1 axis member, leading activation T NK-cells; COM902 an ICI TIGIT....
Abstract Background: While blockade of the CTLA4 and PD1 pathways has emerged as an effective treatment cancer, majority patients do not derive long term benefit. This provides a rationale for identifying targeting additional checkpoints. Employing our unique computational algorithms, we identified PVRIG, new member B7/CD28 family. We report here expression pattern, functional characterization, anti-tumor activity blocking antibodies PVRIG well characterization KO mice. Materials Methods: is...
Meeting abstracts Members of the B7/CD28 family immune checkpoints, such as CTLA4, PD1 and PDL-1, play critical roles in T cell regulation have emerged promising drug targets for cancer immunotherapy. We hypothesize that additional novel members a role
Abstract Poorly immune infiltrated cancers pose a significant challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as cell subgroup which possess enhanced proliferative capacity that could expand and differentiate upon dendritic (DCs) priming. In this study we investigated the expression of recently discovered inhibitory receptor PVRIG its ligand, PVRL2, in tumor microenvironment (TME). Leveraging single RNA...
Abstract IL-18 is an inflammasome induced proinflammatory cytokine that augments T and NK cell activity stimulates IFNγ production. The of naturally blocked by a high affinity endogenous binding protein (IL-18BP). IL-18BP in the tumor microenvironment (TME) response to upregulation negative feedback mechanism. By evaluating 88 human specimens serum samples we were able show upregulated TME (median 11.2ng/gr) compared 0.3ng/ml). Moreover, showed most bound IL-18BP. IL-18BP-bound levels...
<p>Supplemental Figure S3. Antitumor activity of anti-mouse-IL-18BP Ab in mice studies.</p>