A5062402995- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Inflammation biomarkers and pathways
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Asthma and respiratory diseases
- Cancer Immunotherapy and Biomarkers
- CRISPR and Genetic Engineering
- Immune cells in cancer
- PARP inhibition in cancer therapy
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- Pancreatic function and diabetes
- Inflammatory mediators and NSAID effects
- Pluripotent Stem Cells Research
- Parkinson's Disease Mechanisms and Treatments
- Telomeres, Telomerase, and Senescence
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Cardiovascular Syncope and Autonomic Disorders
- Cytomegalovirus and herpesvirus research
- Botulinum Toxin and Related Neurological Disorders
- FOXO transcription factor regulation
Yale University
2019-2025
Dysautonomia Foundation
2020
New York University
2016-2020
New York Oncology Hematology
2019
Universidad de Navarra
2012-2017
Clinica Universidad de Navarra
2012-2016
Cellular senescence has emerged as a potent tumor suppressor mechanism in numerous human neoplasias. Senescent cells secrete distinct set of factors, collectively termed the senescence-associated secretory phenotype (SASP), which been postulated to carry both pro- and antitumorigenic properties depending on tissue context. However, vivo effect SASP is poorly understood due difficulty studying independently other phenotypes. Here, we report that disruption interleukin-1 (IL-1) pathway...
To evaluate the tissue distribution and clinical significance of OX40 OX40L in human non-small cell lung cancer (NSCLC).Using multiplexed quantitative immunofluorescence, we conducted simultaneous localized measurements proteins, major T-cell subsets, conventional type 1 dendritic cells (cDC1) 614 primary NSCLCs from three independent cohorts represented microarrays. We also measured protein samples a phase I trial intratumor administration lipid nanoparticle encapsulated mRNA encoding...
The tumor microenvironment (TME) in solid tumors contains myeloid cells that modulate local immune activity. STING signaling activation these enhances type I interferon (IFN) production, inducing an innate response mobilizes adaptive immunity and reprograms immunosuppressive populations to drive antitumor immunity. Here, we generated TAK-500, cell directed antibody drug conjugate (iADC), deliver a agonist CCR2+ human enhanced activity relative non-targeted agonists. Preclinically, TAK-500...
<p>Conjugation enhances potency compared with dazostinag through selective delivery to immune cells and improved PK. <b>A,</b> Structure of STING agonist TAK-500. <b>B,</b> Receptor occupancy (RO) assessment in human (left) murine (right) whole blood; EC<sub>50</sub> values 1.757 ± 0.524 1.386 1.151 µg/mL, respectively. Data shown represent the mean five donors from a single experiment. Experiment was performed at least twice consistent results...
<p>mTAK-500 shows durable enhanced efficacy and increased activation of innate adaptive immune responses when combined with anti–PD-1 or radiation. <b>A,</b> Antitumor effect mTAK-500 without αPD-1 therapy in C57BL/6 mice bearing MC38 tumors. Data shown represent the MTVs from eight per group. <b>B,</b> Evaluation immune-cell blood, lymph nodes, tumors tumor–bearing treated αPD-1. mean five group timepoint. <b>C,</b> 8 Gy focal radiation treatment...
<p>Evaluation of CCR2 expression levels and the impact TAK-500 treatment on T NK cell activation cytokine production in vitro.</p>
<p>Gating Strategy for Murine Macrophage/Dendritic Cell Panel</p>
<p>Gating Strategy for Evaluating T and NK Cell Activation</p>
<p>TAK-500 drives activation of monocytes and induces type-I IFN response <i>in vitro.</i><b>A,</b> Evaluation classical monocyte frequency (left), (middle), CCR2 expression (right) in PBMCs treated with TAK-500 for 24 hours. Data shown indicate the results five human donors from a single experiment. Experiment was performed at least twice consistent between independent replicates. <b>B,</b> Cytokine induction whole blood after treatment represent...
<p>Evaluation of CCR2 expression in intratumoral mMDSCs within syngeneic tumor bearing mouse models via flow cytometry correlated with the antitumor response those to mTAK-500. Models evaluated include C1498, B16F10, MC38, H22, CT26, JC, and Panc02.</p>
<p>Analysis of TAK-500 iADC.</p>
<p>Binding Curves Demonstrate Species Specificity for antibody portions of TAK-500 and mTAK-500</p>
<p>Gating Strategy for Receptor Occupancy in Human Whole Blood</p>
<p>Gating Strategy for Receptor Occupancy in Murine Whole Blood</p>