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28 results on '"Tracey, Shannon"'

1. The development of next-generation nanoparticle delivery systems using variable new antigen receptors for the treatment of cancer

Author

Tracey, Shannon, Longley, Daniel, and Scott, Christopher

Subjects
Nanomedicine, vNAR, biologics, cancer, tumour targeting
Abstract

With a growing knowledge of the biology of cancer, a range of potential new drug targets have been identified, many of which are intracellular or difficult to target. Monoclonal antibodies and their derivatives have transformed the field of oncology, with monoclonal antibodies a current gold standard treatment both as single agents and  in combination with other therapeutic approaches. However, their use is often limited, with targeting only successful for those antigens/receptors expressed on the cell surface. Consequently, those targets which are expressed intracellularly lack a viable targeting option. Thus, novel approaches to target cancer oncogenes, both intracellular and extracellular, are required. This thesis, in collaboration with Elasmogen Ltd, pioneers of vNAR technology, aims to outline the potential of vNARs as novel therapeutic agents to bind to and inhibit both intracellular oncogenes, in addition to exploring extracellular proteins as targets. Possessing remarkable stability, far superior to that of antibodies or fragments and an ability to bind cryptic/hidden epitopes with high affinity, it is hypothesised that vNARs may be ideally suited not only to inhibiting the activity of these intracellular antigens, but as promising alternatives to monoclonal antibodies in targeting cell surface proteins. One of the most pertinent challenges affecting drug development, is the ability to control the biological fate of the active pharmaceutical ingredient (API) following administration. Therefore, this thesis illustrates the isolation and evaluation of novel vNAR binders towards a panel of both intracellular and extracellular targets for application in the treatment of cancer. Isolated vNARs were evaluated for development into a novel vNAR-conjugated, nanoparticle-based delivery systems for superior delivery of cytotoxic payloads. Alongside this, a cationic nanoparticle delivery system was developed to facilitate enhanced cellular uptake and intracellular cargo delivery.

Published
2022

3. Modular Semisynthetic Approach to Generate T Cell-Dependent Bispecific Constructs from Recombinant IgG1 Antibodies

Author

Shajan, Irene, Rochet, Léa N.C., Tracey, Shannon R., Benazza, Rania, Jackowska, Bianka, Hernandez-Alba, Oscar, Cianférani, Sarah, Scott, Christopher J., van Delft, Floris L., Chudasama, Vijay, Albada, Bauke, Shajan, Irene, Rochet, Léa N.C., Tracey, Shannon R., Benazza, Rania, Jackowska, Bianka, Hernandez-Alba, Oscar, Cianférani, Sarah, Scott, Christopher J., van Delft, Floris L., Chudasama, Vijay, and Albada, Bauke

Abstract

Redirecting T cells to tumor cells by bispecific antibodies is an effective approach to treat cancer, and T cell-dependent bispecific antibodies (TDBAs) are an emerging class of potent immunotherapeutic agents. By simultaneously targeting antigens on tumor cells and T cells, T cells are activated to kill tumor cells. Herein, we report a platform to generate a novel class of 2:1 structure of T cell-dependent bispecific antibody with bivalency for HER2 receptors on tumor cells and monovalency for CD3 receptors on T cells. For this, we use a biogenic inverse electron-demand Diels-Alder (IEDDA) click reaction on genetically encoded tyrosine residues to install one TCO handle on therapeutically approved antibody trastuzumab. Subsequent TCO-tetrazine click with a tetrazine-functionalized CD3-binding Fab yields a 2:1 HER2 × CD3 TDBA that exhibits a tumor-killing capability at picomolar concentrations. Monovalency toward the CD3 receptor on T cells can lower the chances of cytokine release syndrome, which is a common side effect of such agents. Our semisynthetic approach can generate highly potent TDBA constructs in a few chemoenzymatic and synthetic steps.

Published
2024

5. Rapid Access to Potent Bispecific T Cell Engagers Using Biogenic Tyrosine Click Chemistry

Author

Shajan, Irene, Rochet, Léa, Tracey, Shannon, Jackowska, Bianka, Benazza, Rania, Hernandez-Alba, Oscar, Cianférani, Sarah, Scott, Christopher, van Delft, Floris, Chudasama, Vijay, Albada, Bauke, Shajan, Irene, Rochet, Léa, Tracey, Shannon, Jackowska, Bianka, Benazza, Rania, Hernandez-Alba, Oscar, Cianférani, Sarah, Scott, Christopher, van Delft, Floris, Chudasama, Vijay, and Albada, Bauke

Abstract

Bispecific antibodies as T cell engagers designed to display binding capabilities to both tumor-associated antigens and antigens on T cells are considered promising agents in the fight against cancer. Even though chemical strategies to develop such constructs have emerged, a method that readily converts a therapeutically applied antibody into a bispecific construct by a fully non-genetic process is not yet available. Herein, we report the application of a biogenic, tyrosine-based click reaction utilizing chemoenzymatic modifications of native IgG1 antibodies to generate a synthetic bispecific antibody construct that exhibits tumor-killing capability at picomolar concentrations. Control experiments revealed that a covalent linkage of the different components is required for the observed biological activities. In view of the highly potent nature of the constructs and the modular approach that relies on convenient synthetic methods utilizing therapeutically approved biomolecules, our method expedites the production of potent bispecific antibody constructs with tunable cell killing efficacy with significant impact on therapeutic properties.

Published
2023

9. Microbes versus fish : the bioenergetics of coral reef systems

Author

McDole, Tracey Shannon

Subjects
Dissertations, Academic Biology. (Discipline) UCSD, Dissertations Academic as Topic
Abstract

Metabolic rate refers to the rate by which chemical energy is converted into biological energy and used for either maintenance of existing structure or production of new biomass. The Metabolic Theory of Ecology (MTE) predicts the metabolic rate of individual organisms based on the observation that most variation in an individual's metabolic rate can be explained by body size and temperature. The objective of this dissertation was to investigate the bioenergetics of coral reef systems using MTE. My hypothesis was that human activities alter the energy budget of the reef system, specifically by altering the allocation of metabolic energy between microbes and macrobes. I found that in reef systems, even a small increase in microbial biomass can result in substantial changes in whole system rates of energy and materials flux. By comparison, relatively large reductions in fish biomass, affect the system bioenergetics to a lesser degree. The percentage of the combined fish and microbial predicted metabolic rate that is microbial, a.k.a. the microbialization score, was used as a metric for assessing and comparing reef health. My results demonstrated a strong positive correlation between reef microbialization scores and human impact. Regardless of oceanographic context, the microbialization score was a powerful metric for assessing the level of human impact a reef system is experiencing. The process of microbialization was further examined by assessing the effects of human activity on the relative roles of heterotrophic and autotrophic microbes. I found that shifts in microbial trophic structure change both the magnitude and efficiency of energy flow. Specifically, there was a significant increase in the ratio of autotrophic to heterotrophic microbes with human impact, which was also related to an increase in the mass specific energy requirements (W g-1) of the microbial community. I am proposing that microbialization is actually a mechanism of reef resilience that dampens the effects of both overfishing and eutrophication. In conclusion, this research sheds new light on the effects that rising human impact has on the bioenergetics of coral reef systems and adds to our current understanding of the mechanism(s) that underlie reef system degradation

Published
2012

11. Development of next generation nanomedicinebased approaches for the treatment of cancer: we've barely scratched the surface.

Author

Tracey, Shannon R., Smyth, Peter, Barelle, Caroline J., and Scott, Christopher J.

Subjects
*CANCER treatment, *INDIVIDUALIZED medicine, *NANOMEDICINE, *CANCER cells, *TREATMENT effectiveness
Abstract

Interest in nanomedicines has grown rapidly over the past two decades, owing to the promising therapeutic applications they may provide, particularly for the treatment of cancer. Personalised medicine and 'smart' actively targeted nanoparticles represent an opportunity to deliver therapies directly to cancer cells and provide sustained drug release, in turn providing overall lower off-target toxicity and increased therapeutic effi- cacy. However, the successful translation of nanomedicines from encouraging pre-clinical findings to the clinic has, to date, proven arduous. In this review, we will discuss the use of nanomedicines for the treatment of cancer, with a specific focus on the use of polymeric and lipid nanoparticle delivery systems. In particular, we examine approaches exploring the surface functionalisation of nanomedicines to elicit active targeting and therapeutic effects as well as challenges and future directions for nanoparticles in cancer treatment. [ABSTRACT FROM AUTHOR]

Published
2021
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12. Refined construction of antibody-targeted nanoparticles leads to superior antigen binding and enhanced delivery of an entrapped payload to pancreatic cancer cells

Author

Greene, Michelle K., primary, Nogueira, João C. F., additional, Tracey, Shannon R., additional, Richards, Daniel A., additional, McDaid, William J., additional, Burrows, James F., additional, Campbell, Katrina, additional, Longley, Daniel B., additional, Chudasama, Vijay, additional, and Scott, Christopher J., additional

Published
2020
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16. Additional file 1: of Public health emergency preparedness: a framework to promote resilience

Author

Khan, Yasmin, O’Sullivan, Tracey, Adalsteinn Brown, Tracey, Shannon, Gibson, Jennifer, Généreux, Mélissa, Henry, Bonnie, and Schwartz, Brian

Subjects
human activities, behavioral disciplines and activities, humanities, health care economics and organizations
Abstract

Current study in relation to overarching aim to advance performance measurement for public health emergency preparedness. (DOCX 27 kb)

Published
2018
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19. Organizational Resilience Indicators Based on a Salutogenic Orientation

Author

Tracey, Shannon

Subjects
Business Continuity Planning, Indicators, Organizational Resilience, Salutogenesis
Abstract

Disasters such as the recent parliament shooting in Ottawa, Superstorm Sandy, and the Great Japan Sea Earthquake and tsunami are reminders of the roles essential service organizations have in maintaining public health. On a daily basis, organizations are expected to operate under normal conditions, providing goods, services, and community supports. In crisis situations, it is critical that these organizations continue to operate and contribute to adaptive response and recovery in a community. Business continuity planning focuses on ensuring continued functioning of core operations during a disruption. Inherent to the business continuity field is a prevent-and-protect approach to preparedness activities. Asset-mapping exercises have the potential to balance the predominantly risk-based field by focusing on the strengths and capabilities already present within an organization. To understand the value of asset-mapping activities in business continuity plans (BCPs), indicators for organizational resilience are needed. Indicators have the potential to provide essential service organizations with a way to gauge the value of their BCP activities. In addition, this information can help guide decision-makers when developing BCPs. This research is part of a larger project at the University of Ottawa focused on building the empirical evidence base for BCPs and organizational resilience. This thesis, as a sub-study within the larger project, explores assets and indicators for organizational resilience to contribute to the effective evaluation and engagement of organizations in business continuity planning efforts. Emergent themes highlight the importance of assets and their contribution to the adaptive capacity of an organization in the event of a disaster. This study also provides an example list of 28 SMARTT organizational resilience indicators directly derived from organizational assets, providing information that researchers and essential service organizations can use to evaluate business continuity planning activities in relation to organizational resilience.

Published
2015
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20. IMPACT OF PRE-IMPLANTATION BALLOON VALVULOPLASTY ON PARAVALVULAR AORTIC REGURGITATION IN PATIENTS UNDERGOING BALLOON EXPANDABLE TRANSCATHETER AORTIC VALVE REPLACEMENT

Author

Shing Chiu Wong, Geoffrey Bergman, Ryan Kaple, Dmitriy N. Feldman, Arash Salemi, Harsimran Singh, Robert M. Minutello, Sumeet Pawar, Luke K. Kim, Fay Y. Lin, Rajesh V. Swaminathan, Richard B. Devereux, Tracey Shannon, Dolores Reynolds, and James K. Min

Subjects
medicine.medical_specialty, Transcatheter aortic, business.industry, medicine.medical_treatment, Regurgitation (circulation), Balloon valvuloplasty, Balloon expandable stent, Valve replacement, Internal medicine, medicine, Cardiology, In patient, business, Cardiology and Cardiovascular Medicine
Published
2014
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21. LEFT VENTRICULAR REMODELING FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT IS MORE FAVORABLE IN PATIENTS WITH NO SIGNIFICANT PARAVALVULAR AORTIC REGURGITATION VERSUS THOSE WITH MILD PARAVALVULAR AORTIC REGURGITATION

Author

Shing Chiu Wong, Evelyn M. Horn, Richard B. Devereux, Dmitriy N. Feldman, Fay Y. Lin, Robert M. Minutello, Amiran Baduashvili, Karl H. Krieger, Arash Salemi, Luke K. Kim, Geoffrey Bergman, Polydoros N. Kampaktsis, Tracey Shannon, and Dolores Reynolds

Subjects
medicine.medical_specialty, Transcatheter aortic, business.industry, medicine.medical_treatment, Regurgitation (circulation), medicine.disease, Valve replacement, Internal medicine, medicine, Cardiology, In patient, Cardiology and Cardiovascular Medicine, Ventricular remodeling, business
Published
2013
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28. Modular Semisynthetic Approach to Generate T Cell-Dependent Bispecific Constructs from Recombinant IgG1 Antibodies.

Author

Shajan I, Rochet LNC, Tracey SR, Benazza R, Jackowska B, Hernandez-Alba O, Cianférani S, Scott CJ, van Delft FL, Chudasama V, and Albada B

Abstract

Redirecting T cells to tumor cells by bispecific antibodies is an effective approach to treat cancer, and T cell-dependent bispecific antibodies (TDBAs) are an emerging class of potent immunotherapeutic agents. By simultaneously targeting antigens on tumor cells and T cells, T cells are activated to kill tumor cells. Herein, we report a platform to generate a novel class of 2:1 structure of T cell-dependent bispecific antibody with bivalency for HER2 receptors on tumor cells and monovalency for CD3 receptors on T cells. For this, we use a biogenic inverse electron-demand Diels-Alder (IEDDA) click reaction on genetically encoded tyrosine residues to install one TCO handle on therapeutically approved antibody trastuzumab. Subsequent TCO-tetrazine click with a tetrazine-functionalized CD3-binding Fab yields a 2:1 HER2 × CD3 TDBA that exhibits a tumor-killing capability at picomolar concentrations. Monovalency toward the CD3 receptor on T cells can lower the chances of cytokine release syndrome, which is a common side effect of such agents. Our semisynthetic approach can generate highly potent TDBA constructs in a few chemoenzymatic and synthetic steps.

Published
2024
Full Text
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