A5003844260- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Radiopharmaceutical Chemistry and Applications
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- SARS-CoV-2 and COVID-19 Research
- Cancer, Stress, Anesthesia, and Immune Response
- Advanced Breast Cancer Therapies
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Medical Imaging Techniques and Applications
- Chronic Kidney Disease and Diabetes
- Galectins and Cancer Biology
- Single-cell and spatial transcriptomics
Stanford University
2014-2025
Stanford Medicine
2020
Hebrew University of Jerusalem
2010-2017
Tel Aviv University
2016
Stratford University
2014-2015
Hadassah Medical Center
2012
Significance Antibodies that block the negative signals between PD1-Ligand on tumor cells and PD-1 T are effective therapies against several types of cancer. Ibrutinib, a covalent inhibitor BTK is an approved therapy for B-cell leukemia lymphoma. But ibrutinib also inactivates ITK, enzyme required certain subsets lymphocytes (Th2 cells). We found combination anti–PD-L1 antibodies led to impressive therapeutic effects not only in animal models lymphoma but, surprisingly, breast cancer colon...
Activation of TLR9 by direct injection unmethylated CpG nucleotides into a tumor can induce therapeutic immune response; however, Tregs eventually inhibit the antitumor response and thereby limit power cancer immunotherapies. In tumor-bearing mice, we found that within preferentially express cell surface markers CTLA-4 OX40. We show intratumoral coinjection anti–CTLA-4 anti-OX40 together with depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed low doses...
In situ vaccination with low doses of TLR ligands and anti-OX40 antibodies can cure widespread cancers in preclinical models.
Activation of TLR9 by direct injection unmethylated CpG nucleotides into a tumor can induce therapeutic immune response; however, Tregs eventually inhibit the antitumor response and thereby limit power cancer immunotherapies. In tumor-bearing mice, we found that within preferentially express cell surface markers CTLA-4 OX40. We show intratumoral coinjection anti-CTLA-4 anti-OX40 together with depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed low doses...
Treatment with cetuximab, an EGFR-targeting IgG1 mAb, results in beneficial, yet limited, clinical improvement for patients head and neck (HN) cancer as well colorectal (CRC) WT KRAS tumors. Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells contributes to the efficacy of cetuximab. The costimulatory molecule CD137 (4-1BB) is expressed following memory T cell activation. We found that isolated human substantially increased expression when exposed cetuximab-coated,...
In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies. Intratumoral vaccine administration is thought activate a T cell–mediated immune response, which begins in the treated tumor cascades systemically. this study, we describe PET tracer (64Cu-DOTA-AbOX40) that enabled noninvasive longitudinal imaging of OX40, cell-surface marker cell activation. We report spatiotemporal dynamics activation...
The SARS-CoV-2 pandemic has necessitated the rapid development of prophylactic vaccines. Two mRNA vaccines have been approved for emergency use by FDA and demonstrated extraordinary effectiveness. success these establishes speed therapeutic potential mRNA. These authorized encode full-length versions spike protein. They are formulated with lipid nanoparticle (LNP) delivery vehicles that inherent immunostimulatory properties. Different vaccination strategies alternative would be desirable to...
The combination of the synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses upon co-injection into tumor microenvironment, eradicating simultaneous untreated sites metastatic disease. Here we explore application this in situ immunotherapy to neoadjuvant setting. Current checkpoint blockade therapy is delivered systemically, resulting off-target adverse effects. In contrast, intratumoral minimizes potential for toxicities allows greater...
Antitumor T cell responses are the primary mediators of cancer immunotherapy. However, many other components immune system needed for efficient to be generated. Here, we developed a combinatorial approach where Toll-like receptor 9 agonist (CpG) and Fc-fused IL-12 protein were injected together into just one several tumor sites in mouse. This combination led body-wide (abscopal) therapeutic multiple models. These systemic dependent not only on cells but also B cells. activated by treatment...
Summary VISTA is a key immune checkpoint receptor under investigation for cancer immunotherapy; however, its signaling mechanisms remain unclear. Here we identify conserved four amino acid (NPGF) intracellular motif in that suppresses cell proliferation by constraining cell-intrinsic growth signaling. The NPGF binds to the adapter protein NUMB and recruits Rab11 endosomal recycling machinery. We characterize class of triple-negative breast cancers with high expression low proliferative...
3017 Background: Anti-CD137 antibody was shown in both murine cancer models and a first-in-human, phase I trial (Sznol et al., 2008) to increase peripheral activated CD8 T cells IFN-inducible genes, thereby facilitating cytolytic, antitumor, Th1 response. A multiparametric immune pharmacodynamic assessment of the effects anti-CD137 therapy has not been previously performed. Methods: We employed novel technology mass cytometry time flight (CyTOF) investigate patient's global status prior...
Advanced diagnostic tools stand today at the heart of successful cancer treatment. CellDetect(R) is a new histochemical staining technology that enables color discrimination between normal cells and wide variety neoplastic tissues. Using this technology, are colored blue/green, while red. This tinctorial difference coincides with clear morphological visualization properties, mainly in tissue samples. Here we show can be deployed to distinguish from transformed most significantly detect their...
Meeting abstracts Oncolytic virotherapy is safe and clinically active in solid tumors, however its efficacy hematologic malignancies as well combination with checkpoint inhibitors radiation unexplored. To simulate advanced lymphoma, A20 cells were injected subcutaneously on
Abstract Introduction: Tumor irradiation induces innate and adaptive immune responses which, rarely, lead to tumor regression at distant sites, the abscopal effect. We have previously demonstrated that immunotherapy including Toll-like-receptor agonists (CpG) checkpoint inhibitors (anti-CTLA4) both preclinically clinically (NCT00185965 & NCT01769222) can significantly increase rate of systemic, (Kim, Blood 2012 Brody, JCO 2010). Here we provide first report a preclinical murine model...