Use of a Listeria Monocytogenes Protein to Stimulate Immune Responses and Anti-tumor Effects

Use of a Listeria Monocytogenes Protein to Stimulate Immune Responses and Anti-tumor Effects

Author: Amber Leigh Ortiz

Publisher:

Published: 2017

Total Pages: 149

ISBN-13: 9780355601480

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Natural killer (NK) cells are a type of innate immune cell that secrete IFN when activated. IFN has pro-inflammatory effects and can act on tumor cells to kill them or inhibit their proliferation. NK cells can also exert direct anti-tumor cytolytic activity. Previous work showed that the Listeria monocytogenes (Lm) p60 protein indirectly promotes activation of NK cells to mediate cytokine production. The p60 protein contains two divergent LysM domains and one SH3 domain. The LysM1 domain is responsible for the immune stimulatory activity of the p60 protein and is present with the SH3 domain in a fragment of p60 termed "L1S." Like p60, recombinant L1S binds dendritic cells (DC) to stimulate their secretion of cytokines such as interleukin-18 (IL-18) and license them to promote activation of NK cells. The studies in this thesis investigated the nature of immune cell activation by L1S in vitro and in vivo through direct lung instillation. I found that instillation with wildtype L1S induced recruitment of inflammatory neutrophils and promoted accumulation of activated, IFN-producing, NK cells with increased cytolytic activity. I further showed that instillation of tumor-bearing mice with wildtype L1S protein significantly reduced burdens of established tumors. IFN and NK cells were required for these therapeutic effects. Further studies utilized simulated structure analysis and site-directed mutagenesis to explore the effects of specific amino acids in the LysM1 domain on the function of recombinant L1S protein. Specific amino acids in the LysM1 region were identified as critical for eliciting NK cell activity. Thus, my studies have improved our understanding of L1S immunostimulatory function and demonstrated its potential in vivo use for stimulation of NK cell anti-tumor responses.


Handbook of Listeria Monocytogenes

Handbook of Listeria Monocytogenes

Author: Dongyou Liu

Publisher: CRC Press

Published: 2008-04-21

Total Pages: 554

ISBN-13: 1420051415

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Once feared as a deadly intracellular bacterium with the extraordinary capacity to survive a wide array of arduous external stressors, Listeria monocytogenes is increasingly recognized as a preferred vector for delivering anti-infective and anti-cancer vaccine molecules. A reliable, single-source reference on the fundamental aspects of


Emerging Cancer Therapy

Emerging Cancer Therapy

Author: Arsenio Fialho

Publisher: John Wiley & Sons

Published: 2010-12-07

Total Pages: 536

ISBN-13: 1118035186

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Explores current and emerging applications of microbes as cancer-fighting agents WILEY SERIES IN BIOTECHNOLOGY AND BIOENGINEERING Anurag S. Rathore, Series Editor Today, treatment options for cancer patients typically include surgery, radiation therapy, immunotherapy, and chemotherapy. While these therapies have saved lives and reduced pain and suffering, cancer still takes millions of lives every year around the world. In recent years, researchers have been working on a new strategy: developing microbes and microbial products that specifically attack cancer cells. This book breaks new ground in emerging cancer treatment modalities by presenting recent advances in the use of microorganisms and viruses as well as their products in cancer therapy. Seventeen chapters review the application of live microorganisms, high and low molecular weight products derived from microorganisms, and microbial products fused to cancertargeting molecules. In addition, the book highlights the benefits of a multi-target approach to destroy cancer cells. Readers will not only discover the results and significance of basic and clinical research, but also encouraging results from clinical trials. Emerging Cancer Therapy is divided into three sections: Section 1: Live/Attenuated Bacteria and Viruses as Anticancer Agents Section 2: Bacterial Products as Anticancer Agents Section 3: Patents on Bacteria/Bacterial Products as Anticancer Agents With chapters written by leading pioneers in microbial, biotech, and cancer research, Emerging Cancer Therapy is recommended for biotechnologists, microbiologists, clinical oncologists, medicinal chemists, and biochemists. Readers will not only learn the tremendous potential of microbial and biotechnological approaches to cancer therapy, but also discover new directions of research for effective drug discovery and development.


Oncologic Therapies

Oncologic Therapies

Author: Everett E. Vokes

Publisher: Springer Science & Business Media

Published: 2011-06-28

Total Pages: 686

ISBN-13: 3642557805

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This second edition has been updated in a user-friendly layout that makes its comprehensive information extremely accessible. The handbook, written for all physicians who treat cancer patients, provides a survey of current therapeutic concepts of solid tumors and hematologic malignancies in internal oncology. Each individual chapter of this shortened new edition is structured in the same way and features a brief outline or tabular summary of the main aspects of epidemiology, pathology, staging, and diagnosis. The main focus is on the therapeutic strategy, i.e., an interdisciplinary approach to systemic drug therapy. Surgical and radiological concepts of treatment are also covered, as are supportive care, pain relief methods and ethical problems. This title is a must for clinicians and practitioners as well as interns, residents and postgraduate students.


Immunotherapy – A Novel Facet of Modern Therapeutics

Immunotherapy – A Novel Facet of Modern Therapeutics

Author: Sujata P. Sawarkar

Publisher: Springer Nature

Published: 2020-12-16

Total Pages: 267

ISBN-13: 9811590389

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This book illustrates the significance and relevance of immunotherapy in modern-day therapeutics. Focusing on the application of immunotherapy in oncology, neurodegenerative and autoimmune diseases, it discusses the drug delivery systems, and pre-clinical and clinical methodologies for immunotherapy-based drugs. It also comprehensively reviews various aspects of immunotherapy, such as regulatory affairs, quality control, safety, and pharmacovigilance. Further, the book discusses the in vitro validation of therapeutic strategies prior to patient application and management of immunotherapy-related side effects and presents case studies demonstrating the design and development (pre-clinical to clinical) of immunotherapy for various diseases. It also describes various design considerations and the scale-up synthesis of immunotherapeutics and screening methods. Lastly, it explores the important aspect of cost-effectiveness and rational immunotherapy strategies.


Biomaterials for Cancer Therapeutics

Biomaterials for Cancer Therapeutics

Author: Kinam Park

Publisher: Woodhead Publishing

Published: 2020-03-05

Total Pages: 783

ISBN-13: 0081029845

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Biomaterials for Cancer Therapeutics: Evolution and Innovation, Second Edition, discusses the role and potential of biomaterials in treating this prevalent disease. The first part of the book discusses the fundamentals of biomaterials for cancer therapeutics. Part Two discusses synthetic vaccines, proteins and polymers for cancer therapeutics. Part Three focuses on theranosis and drug delivery systems, while the final set of chapters look at biomaterial therapies and cancer cell interaction. Cancer affects people of all ages, and approximately one in three people are estimated to be diagnosed with cancer during their lifetime. Extensive research is being undertaken by many different institutions to explore potential new therapeutics, and biomaterials technology is being developed to target, treat and prevent cancer. Hence, this book is a welcomed resource to the discussion. Provides a complete overview of the latest research into the potential of biomaterials for the diagnosis, treatment and prevention of cancer Discusses how the properties of specific biomaterials make them important in cancer treatment Covers synthetic vaccines, proteins and polymers for cancer therapeutics


Gene and Cell Therapy

Gene and Cell Therapy

Author: Nancy Smyth Templeton

Publisher: CRC Press

Published: 2003-12-17

Total Pages: 894

ISBN-13: 0824758609

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This reference is completely revised and expanded to reflect the most critical studies, controversies, and technologies impacting the medical field, including probing research on lentivirus, gutless adenovirus, bacterial and baculovirus vectors, retargeted viral vectors, in vivo electroporation, in vitro and in vivo gene detection systems, and all inducible gene expression systems. Scrutinizing every tool, technology, and issue impacting the future of gene and cell research, it is specifically written and organized for laymen, scholars, and specialists from varying backgrounds and disciplines to understand the current status of gene and cell therapy and anticipate future developments in the field.