A5049267853- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Photodynamic Therapy Research Studies
- Nanoplatforms for cancer theranostics
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- Retinoids in leukemia and cellular processes
- Atherosclerosis and Cardiovascular Diseases
- Cancer, Lipids, and Metabolism
- CRISPR and Genetic Engineering
- Radiopharmaceutical Chemistry and Applications
- Extracellular vesicles in disease
- Lysosomal Storage Disorders Research
- Lanthanide and Transition Metal Complexes
- Transgenic Plants and Applications
- Metabolomics and Mass Spectrometry Studies
- Inflammasome and immune disorders
- Calcium signaling and nucleotide metabolism
- Cerebrovascular and Carotid Artery Diseases
- interferon and immune responses
- Lipid metabolism and disorders
- Prostate Cancer Treatment and Research
Center for Systems Biology
2017-2024
Massachusetts General Hospital
2017-2024
University of Pennsylvania
2014-2020
Harvard University
2017-2019
Tumor-associated macrophages limit anti–PD-1 effects by removing the antibody from CD8 + T cells.
Tumor-associated macrophages (TAM) have attracted attention as they can modulate key cancer-related activities, yet TAM represent a heterogenous group of cells that remain incompletely characterized. In growing tumors, are often referred to M2-like macrophages, which display immunosuppressive and tumorigenic functions express the enzyme arginase 1 (Arg1). Methods: Here we combined high resolution intravital imaging with single cell RNA seq uncover topography molecular profiles in mice. We...
Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a likelihood response to PD-1 blockade. We conducted prospective multicenter phase II trial intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined pembrolizumab in patients advanced melanoma cytotoxic (cpCTL).Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while (200 mg, i.v.) 3 weeks. The primary endpoint objective rate (ORR) by RECIST,...
Abstract Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation measure tumor fluorescence. Three systems (Spectropen, Glomax, Flocam) measured quantified fluorescent signal-to-background ratios (SBR) vitro , murine xenografts, tissue phantoms clinically. Evaluation criteria included the detection of small changes...
Abstract Abnormal choline metabolism is a hallmark of cancer and associated with oncogenesis tumor progression. Increased consistently observed in both preclinical models human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition using specific kinase inhibitors such as MN58b may be promising new strategy for treatment tumors. We demonstrate the efficacy suppressing phosphocholine production three cell lines. In vivo MRS studies rats intracranial F98-derived showed...
Choline kinase alpha (ChoK) expression is increasingly being recognized as an important indicator of breast cancer prognosis; however, previous efforts to noninvasively measure ChoK status have been complicated by the spectral limitations in vivo magnetic resonance spectroscopy (MRS) and complex network enzymes involved choline metabolism. The most effective inhibitors are symmetric contain quaternary ammonium groups within heterocyclic head connected aliphatic spacer. Characterization these...
LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and currently being tested phase II clinical trials. Here we aimed to further evaluate conditional genetic mouse models of cancer typically resist current treatment options better understand the drug's mode action
Choline kinase alpha (ChoKα) overexpression is associated with an aggressive tumor phenotype. ChoKα inhibitors induce apoptosis in tumors, however validation of their specificity difficult vivo. We report the use optical imaging to assess status cells and vivo using JAS239, a carbocyanine-based inhibitor inherent near infrared fluorescence. JAS239 attenuated choline phosphorylation viability panel human breast cancer cell lines. Antibody blockade prevented cellular retention indicating...
Macrophages are critical regulators of the tumor microenvironment and often present an immuno-suppressive phenotype, supporting growth immune evasion. Promoting a robust pro-inflammatory macrophage phenotype has emerged as therapeutic modality that supports clearance, including through synergy with checkpoint therapies. Polyglucose nanoparticles (macrins), which possess high affinity, useful vehicles for delivering drugs to macrophages, potentially altering their phenotype. Here, we examine...
Macrophages have been associated with drug response and resistance in diverse settings, thus raising the possibility of using macrophage imaging as a companion diagnostic to inform personalized patient treatment strategies.Nanoparticle-based contrast agents are especially promising because they efficiently deliver fluorescent, magnetic, and/or radionuclide labels by leveraging intrinsic capacity macrophages accumulate nanomaterials their role professional phagocytes.Unfortunately, current...
Abstract B cells are an attractive platform for engineering to produce protein-based biologics absent in genetic disorders, and potentially the treatment of metabolic diseases cancer. As part pre-clinical development cell medicines, we demonstrate a method collect, ex vivo expand, differentiate, radioactively label, track adoptively transferred non-human primate (NHP) cells. These underwent 10- 15-fold expansion, initiated IgG class switching, differentiated into antibody secreting...
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