A5033397787- Veterinary Oncology Research
- Cancer Research and Treatments
- Sarcoma Diagnosis and Treatment
- Virus-based gene therapy research
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Angiogenesis and VEGF in Cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CAR-T cell therapy research
- Nausea and vomiting management
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Cancer Treatment and Pharmacology
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Pathogenesis and Treatment of Hiccups
- Silk-based biomaterials and applications
- Chemokine receptors and signaling
- Nanoplatforms for cancer theranostics
- Retinal Diseases and Treatments
- Anesthesia and Pain Management
- Immune Cell Function and Interaction
- Neutropenia and Cancer Infections
- EEG and Brain-Computer Interfaces
- Advancements in Transdermal Drug Delivery
Massachusetts Institute of Technology
2021-2024
Allen Institute
2024
McGovern Institute for Brain Research
2021
Harvard–MIT Division of Health Sciences and Technology
2021
Vaxess Technologies (United States)
2020-2021
Sunnybrook Health Science Centre
2014-2018
Health Sciences Centre
2014-2018
University of Toronto
2015-2017
Tufts University
2015-2016
Abstract Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development a tumor-anchored ɑ4-1BB (ɑ4-1BB-LAIR), which consists antibody fused to collagen-binding protein LAIR. While combination treatment an (TA99) shows only modest efficacy, simultaneous depletion CD4+ boosts cure rates over 90% mice....
Microneedles represent an exciting departure from the existing parenteral injection paradigm for drug delivery, particularly administration of vaccines. While benefit delivering vaccine antigens to immunocompetent tissue in skin has been established, there have varying degrees success using microneedles do so. Here, we investigate use silk fibroin protein produce and evaluate their ability deliver vaccines against influenza, Clostridium difficile, Shigella. Fibroin silkworm Bombyx mori...
Anti-CTLA-4 antibodies have successfully elicited durable tumor regression in the clinic; however, long-term benefit is limited to a subset of patients for select cancer indications. The incomplete understanding their mechanism action has hindered efforts at improvement, with conflicting hypotheses proposing either antagonism CTLA-4:B7 axis or Fc effector-mediated regulatory T cell (Treg) depletion governing efficacy. Here, we report engineering nonantagonistic CTLA-4 binding domain (b1s1e2)...
Systemically administered cytokines are potent immunotherapeutics but can cause severe dose-limiting toxicities. To overcome this challenge, have been engineered for intratumoral retention after local delivery. However, despite inducing regression of treated lesions, tumor-localized often elicit only modest responses at distal untreated tumors. In the present study, we report a localized cytokine therapy that safely elicits systemic antitumor immunity by targeting ubiquitous leukocyte...
<div>Abstract<p>Although heightened intratumoral levels of reactive oxygen species (ROS) are typically associated with a suppressive tumor microenvironment, under certain conditions ROS contribute to elimination. Treatment approaches, including some chemotherapy and radiation protocols, increase cancer cell that influence their mechanism death subsequent recognition by the immune system. Furthermore, activated myeloid cells rapidly generate upon encounter pathogens or infected...
<p>Fluorescence intensities of OT-I phenotypic markers from the cross-presentation assay with IFNa</p>
<p>Bolus hydrogen peroxide is cytotoxic but rapidly cleared by cancer cells</p>
<p>Cross-presentation assay T-cell gating strategy</p>
<p>Comparison of OT-I phenotypes in cross-presentation assay after treatment with immunogenic cell stress-inducing chemotherapy</p>
<p>Cross-presentation assay myeloid cell gating strategy</p>
<p>2.5F-GOX and MSA-IFNa do not cause toxicity in mice but fail to generate anti-tumor memory</p>
<p>Characterization of recombinant glucose oxidase fusions</p>
<p>Protein sequences</p>
<p>Additional flow analysis of 2.5F-GOX dose escalation study</p>
Cytokine therapies such as IL2 and IL12 suffer from impractically small therapeutic windows driven by their on-target, off-tumor activity, limiting clinical potential despite potent antitumor effects. We previously engineered cytokines that bind anchor to tumor collagen following intratumoral injection, sought test safety biomarker activity in spontaneous canine soft-tissue sarcomas (STS).Collagen-binding were canine-ized minimize immunogenicity used a rapid dose-escalation study healthy...
Corticosteroids are used adjuvant to certain chemotherapy regimens, either as an antiemetic, reduce other side effects, or enhance cancer treatment. Additionally, they frequently for symptom control in patients with end stage disease. Corticosteroid use may induce hyperglycemia approximately 20-50% of patients, which negatively affect patient outcomes.To determine the frequency blood glucose monitoring and without diabetes receiving continuous corticosteroids chemotherapy, incidence...
Catalase is an antioxidant enzyme that catalyzes the rapid conversion of hydrogen peroxide to water and oxygen. Use catalase as a cancer therapeutic has been proposed reduce oxidative stress hypoxia in tumor microenvironment, both activities which are hypothesized growth. Furthermore, exposing murine tumors exogenous was previously reported have benefit. We studied effect tumor-localized catalases with aim further elucidate mechanism action. To do this, we engineered two approaches maximize...
Background: While the efficacy of olanzapine in prophylaxis chemotherapy-induced nausea and vomiting (CINV) has been documented, literature on use as a rescue medication for breakthrough CINV scarce. The following study retrospectively evaluated safety treatment CINV. prophylactic setting was also examined smaller cohort. Methods: Electronic medical records adult patients aged >17 years receiving prescription from Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 June...
Thermal drawing has been recently leveraged to yield multifunctional, fiber-based neural probes at near kilometer length scales. Despite its promise, the widespread adoption of this approach impeded by (1) material compatibility requirements and (2) labor-intensive interfacing functional features external hardware. Furthermore, in multifunctional fibers, significant volume is occupied passive polymer cladding that so far only served structural or electrical insulation purposes. In article,...
Cytokines IL2 and IL12 exhibit potent anticancer activity but suffer a narrow therapeutic window due to off-tumor immune cell activation. Engineering cytokines with the ability bind associate tumor collagen after intratumoral injection potentiated response without toxicity in mice was previously safe pet dogs sarcoma. Here, we sought test efficacy of this approach advanced melanoma.