Engineering Protein-based Modulators of Allergic, Temporal, and Checkpoint Blockade Anti-cancer Immunity

Engineering Protein-based Modulators of Allergic, Temporal, and Checkpoint Blockade Anti-cancer Immunity PDF Author: Adrienne Marie Rothschilds
Publisher:
ISBN:
Category :
Languages : en
Pages : 137

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Book Description
Effective cancer treatment of the future requires incorporating diverse and innovative aspects of immunity to fight against cancer, accounting for pharmacokinetic and temporal barriers of therapeutics, and engineering approaches to understand and improve upon current immunotherapies. This thesis addresses these challenges in three projects utilizing the Wittrup Lab's quantitative, engineering approach to protein-based cancer immunotherapy. In the first project, I attempted to harness the potency of allergic reactions against cancer by designing IgE class antibodies against two mouse tumor antigens and comparing them with traditional IgG antibodies. These IgE antibodies elicited modest or no tumor control, and limited efficacy could be due to fast pharmacokinetic clearance, absence of human-like allergic effector cells in mice, or tumor-suppressive effects from mast cells responding to IgE. The second project described in this thesis focused on synchronizing combination immunotherapies with the temporal progression of the anti-cancer immune response. In this work, anti-tumor antibodies were combined with the cytokines interleukin 2 (IL2) and interferon alpha (IFNa). The order of administration of these therapies decoupled strong efficacy from dose-limiting toxicity in two tumor models. Given before IFN[alpha], IL2 activated natural killer cells and heightened their responsiveness to subsequent IFN[alpha], which was ultimately toxic and unnecessary for therapeutic efficacy. This project's proof of concept that efficacy and toxicity could be unlinked in immunotherapy began to establish a framework to use for rational combination therapy treatment schedule design, with the goal of treating with each agent when that piece of the immune system is active. Finally, the third project used the Wittrup Lab's system of yeast surface display to engineer novel antibodies against the checkpoint blockade target cytotoxic T lymphocyte associated protein 4 (CTLA-4) as tools to improve understanding of the anti-CTLA-4 mechanism of action against cancer. Although the first wave of antibodies made had favorable characteristics against CTLA-4 as a soluble target, they bound a CTLA-4 epitope too close to the cell surface and so could not be used for therapeutic studies. Next generation sequencing on the yeast libraries identified alternative CTLA-4 binding antibody sequences, and these will be tested in future mechanistic and therapeutic studies.

Engineering Protein-based Modulators of Allergic, Temporal, and Checkpoint Blockade Anti-cancer Immunity

Engineering Protein-based Modulators of Allergic, Temporal, and Checkpoint Blockade Anti-cancer Immunity PDF Author: Adrienne Marie Rothschilds
Publisher:
ISBN:
Category :
Languages : en
Pages : 137

Get Book Here

Book Description
Effective cancer treatment of the future requires incorporating diverse and innovative aspects of immunity to fight against cancer, accounting for pharmacokinetic and temporal barriers of therapeutics, and engineering approaches to understand and improve upon current immunotherapies. This thesis addresses these challenges in three projects utilizing the Wittrup Lab's quantitative, engineering approach to protein-based cancer immunotherapy. In the first project, I attempted to harness the potency of allergic reactions against cancer by designing IgE class antibodies against two mouse tumor antigens and comparing them with traditional IgG antibodies. These IgE antibodies elicited modest or no tumor control, and limited efficacy could be due to fast pharmacokinetic clearance, absence of human-like allergic effector cells in mice, or tumor-suppressive effects from mast cells responding to IgE. The second project described in this thesis focused on synchronizing combination immunotherapies with the temporal progression of the anti-cancer immune response. In this work, anti-tumor antibodies were combined with the cytokines interleukin 2 (IL2) and interferon alpha (IFNa). The order of administration of these therapies decoupled strong efficacy from dose-limiting toxicity in two tumor models. Given before IFN[alpha], IL2 activated natural killer cells and heightened their responsiveness to subsequent IFN[alpha], which was ultimately toxic and unnecessary for therapeutic efficacy. This project's proof of concept that efficacy and toxicity could be unlinked in immunotherapy began to establish a framework to use for rational combination therapy treatment schedule design, with the goal of treating with each agent when that piece of the immune system is active. Finally, the third project used the Wittrup Lab's system of yeast surface display to engineer novel antibodies against the checkpoint blockade target cytotoxic T lymphocyte associated protein 4 (CTLA-4) as tools to improve understanding of the anti-CTLA-4 mechanism of action against cancer. Although the first wave of antibodies made had favorable characteristics against CTLA-4 as a soluble target, they bound a CTLA-4 epitope too close to the cell surface and so could not be used for therapeutic studies. Next generation sequencing on the yeast libraries identified alternative CTLA-4 binding antibody sequences, and these will be tested in future mechanistic and therapeutic studies.

Biodefense in the Age of Synthetic Biology

Biodefense in the Age of Synthetic Biology PDF Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309465184
Category : Technology & Engineering
Languages : en
Pages : 189

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Book Description
Scientific advances over the past several decades have accelerated the ability to engineer existing organisms and to potentially create novel ones not found in nature. Synthetic biology, which collectively refers to concepts, approaches, and tools that enable the modification or creation of biological organisms, is being pursued overwhelmingly for beneficial purposes ranging from reducing the burden of disease to improving agricultural yields to remediating pollution. Although the contributions synthetic biology can make in these and other areas hold great promise, it is also possible to imagine malicious uses that could threaten U.S. citizens and military personnel. Making informed decisions about how to address such concerns requires a realistic assessment of the capabilities that could be misused. Biodefense in the Age of Synthetic Biology explores and envisions potential misuses of synthetic biology. This report develops a framework to guide an assessment of the security concerns related to advances in synthetic biology, assesses the levels of concern warranted for such advances, and identifies options that could help mitigate those concerns.

Immunotherapy

Immunotherapy PDF Author: Aung Naing
Publisher: Springer Nature
ISBN: 3030793087
Category : Medical
Languages : en
Pages : 445

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Book Description
The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.

Immunopharmacology

Immunopharmacology PDF Author: Manzoor M. Khan
Publisher: Springer Science & Business Media
ISBN: 0387779760
Category : Medical
Languages : en
Pages : 275

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Book Description
During the past decades, with the introduction of the recombinant DNA, hybridoma and transgenic technologies there has been an exponential evolution in understanding the pathogenesis, diagnosis and treatment of a large number of human diseases. The technologies are evident with the development of cytokines and monoclonal antibodies as therapeutic agents and the techniques used in gene therapy. Immunopharmacology is that area of biomedical sciences where immunology, pharmacology and pathology overlap. It concerns the pharmacological approach to the immune response in physiological as well as pathological events. This goals and objectives of this textbook are to emphasize the developments in immunology and pharmacology as they relate to the modulation of immune response. The information includes the pharmacology of cytokines, monoclonal antibodies, mechanism of action of immune-suppressive agents and their relevance in tissue transplantation, therapeutic strategies for the treatment of AIDS and the techniques employed in gene therapy. The book is intended for health care professional students and graduate students in pharmacology and immunology.

Advanced Healthcare Materials

Advanced Healthcare Materials PDF Author: Ashutosh Tiwari
Publisher: John Wiley & Sons
ISBN: 1118773683
Category : Technology & Engineering
Languages : en
Pages : 421

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Book Description
Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers

Guide to Immunotherapy

Guide to Immunotherapy PDF Author: Suzanne L. Walker
Publisher:
ISBN: 9781635930184
Category :
Languages : en
Pages :

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Book Description


Immunopotentiators in Modern Vaccines

Immunopotentiators in Modern Vaccines PDF Author: Virgil Schijns
Publisher: Elsevier
ISBN: 0080457215
Category : Medical
Languages : en
Pages : 396

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Book Description
Immunopotentiators in Modern Vaccines provides an in-depth insight and overview of a number of most promising immunopotentiators in modern vaccines. In contrast to existing books on the subject it provides recent data on the critical mechanisms governing the activity of vaccine adjuvants and delivery systems. Knowledge of immunological pathways and scenarios of the cells and molecules involved is described and depicted in comprehensive illustrations. Contributions from leading international authorities in the field Well-illustrated, informative figures present the interactions between immunopotentiators and the host immune system Each chapter lists advantages and potential hurdles for achieving a practical application for the specific immunopentiator

Fluorescent Nanodiamonds

Fluorescent Nanodiamonds PDF Author: Huan-Cheng Chang
Publisher: John Wiley & Sons
ISBN: 1119477085
Category : Science
Languages : en
Pages : 294

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Book Description
The most comprehensive reference on fluorescent nanodiamond physical and chemical properties and contemporary applications Fluorescent nanodiamonds (FNDs) have drawn a great deal of attention over the past several years, and their applications and development potential are proving to be manifold and vast. The first and only book of its kind, Fluorescent Nanodiamonds is a comprehensive guide to the basic science and technical information needed to fully understand the fundamentals of FNDs and their potential applications across an array of domains. In demonstrating the importance of FNDs in biological applications, the authors bring together all relevant chemistry, physics, materials science and biology. Nanodiamonds are produced by powerful cataclysmic events such as explosions, volcanic eruptions and meteorite impacts. They also can be created in the lab by high-pressure high-temperature treatment of graphite or detonating an explosive in a reactor vessel. A single imperfection can give a nanodiamond a specific, isolated color center which allows it to function as a single, trapped atom. Much smaller than the thickness of a human hair, a nanodiamond can have a huge surface area that allows it to bond with a variety of other materials. Because of their non-toxicity, nanodiamonds may be useful in biomedical applications, such as drug delivery and gene therapy. The most comprehensive reference on a topic of rapidly increasing interest among academic and industrial researchers across an array of fields Includes numerous case studies and practical examples from many areas of research and industrial applications, as well as fascinating and instructive historical perspectives Each chapter addresses, in-depth, a single integral topic including the fundamental properties, synthesis, mechanisms and functionalisation of FNDs The first book published by the key patent holder with his research group in the field of FNDs Fluorescent Nanodiamonds is an important working resource for a broad range of scientists and engineers in industry and academia. It will also be a welcome reference for instructors in chemistry, physics, materials science, biology and related fields.

Drug Repurposing in Cancer Therapy

Drug Repurposing in Cancer Therapy PDF Author: Kenneth K.W. To
Publisher: Academic Press
ISBN: 0128199032
Category : Science
Languages : en
Pages : 460

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Book Description
Drug Repurposing in Cancer Therapy: Approaches and Applications provides comprehensive and updated information from experts in basic science research and clinical practice on how existing drugs can be repurposed for cancer treatment. The book summarizes successful stories that may assist researchers in the field to better design their studies for new repurposing projects. Sections discuss specific topics such as in silico prediction and high throughput screening of repurposed drugs, drug repurposing for overcoming chemoresistance and eradicating cancer stem cells, and clinical investigation on combination of repurposed drug and anticancer therapy. Cancer researchers, oncologists, pharmacologists and several members of biomedical field who are interested in learning more about the use of existing drugs for different purposes in cancer therapy will find this to be a valuable resource. Presents a systematic and up-to-date collection of the research underpinning the various drug repurposing approaches for a quick, but in-depth understanding on current trends in drug repurposing research Brings better understanding of the drug repurposing process in a holistic way, combining both basic and clinical sciences Encompasses a collection of successful stories of drug repurposing for cancer therapy in different cancer types

Nanopharmaceuticals: Principles and Applications Vol. 3

Nanopharmaceuticals: Principles and Applications Vol. 3 PDF Author: Vinod Kumar Yata
Publisher: Springer Nature
ISBN: 3030471209
Category : Technology & Engineering
Languages : en
Pages : 340

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Book Description
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.