Toxin and Immunotoxin Based Therapeutic Approaches

Toxin and Immunotoxin Based Therapeutic Approaches PDF Author: Massimo Bortolotti
Publisher:
ISBN: 9783036530659
Category :
Languages : en
Pages : 122

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Book Description
In 1900, Paul Ehrlich, who was studying ricin and abrin at the time, discovered antibodies and paved the way for immunotherapy. After 120 years, Ehrlich's insight into the therapeutic potential of immunotargeting is still a source of inspiration for many scientists. One of the most studied antibody-based targeting strategies is the carrying of powerful toxins. The generated molecules are immunotoxins, i.e., chimeric proteins obtained by coupling bacterial or plant toxins and antibodies through chemical linking or genetic engineering. Immunotoxins are functionally designed to eliminate the cells responsible for pathological conditions, and they find applications in several fields, ranging from cancer to immunological diseases or pain control. Despite the lack of specificity, even native toxins find clinical application, but the use of unconjugated toxins is limited to loco-regional treatments. A fundamental requirement for the medical application of toxins and their immunoconjugates is in-depth knowledge of their interaction with target cells in terms of binding, uptake, intracellular routing, and substrate specificity. This Special Issue focuses on toxins and immunotoxins that have clinical potential. We hope to give the reader a comprehensive overview of new toxin delivery strategies and toxin-based experimental disease models, both in vitro and in vivo.

Toxin and Immunotoxin Based Therapeutic Approaches

Toxin and Immunotoxin Based Therapeutic Approaches PDF Author: Massimo Bortolotti
Publisher:
ISBN: 9783036530659
Category :
Languages : en
Pages : 122

Get Book Here

Book Description
In 1900, Paul Ehrlich, who was studying ricin and abrin at the time, discovered antibodies and paved the way for immunotherapy. After 120 years, Ehrlich's insight into the therapeutic potential of immunotargeting is still a source of inspiration for many scientists. One of the most studied antibody-based targeting strategies is the carrying of powerful toxins. The generated molecules are immunotoxins, i.e., chimeric proteins obtained by coupling bacterial or plant toxins and antibodies through chemical linking or genetic engineering. Immunotoxins are functionally designed to eliminate the cells responsible for pathological conditions, and they find applications in several fields, ranging from cancer to immunological diseases or pain control. Despite the lack of specificity, even native toxins find clinical application, but the use of unconjugated toxins is limited to loco-regional treatments. A fundamental requirement for the medical application of toxins and their immunoconjugates is in-depth knowledge of their interaction with target cells in terms of binding, uptake, intracellular routing, and substrate specificity. This Special Issue focuses on toxins and immunotoxins that have clinical potential. We hope to give the reader a comprehensive overview of new toxin delivery strategies and toxin-based experimental disease models, both in vitro and in vivo.

Chimeric Toxins

Chimeric Toxins PDF Author: Haya Lorberboum-Galski
Publisher: CRC Press
ISBN: 1134454546
Category : Medical
Languages : en
Pages : 448

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Book Description
Bacteria and plants produce powerful toxins that can cause a variety of diseases, some of which are lethal for many animal species. The mechanisms of action are common to many of these toxins and represent general pathways for the interaction of a number of biomolecules with target cells, such as binding to specific surface receptors, internalizati

Clinical Applications of Immunotoxins

Clinical Applications of Immunotoxins PDF Author: Arthur E. Frankel
Publisher: Springer
ISBN: 9783642721540
Category : Medical
Languages : en
Pages : 122

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Book Description
1 2 D. FITZGERALDI, I. PASTAN , and J. ROBERTUS Introduction . . . . . . . . . . . . . I 2 Toxin Structure-Function Properties 2 2. 1 Functions. . . . . . . . . . . . . . . . . . . . . . . . 2 2. 2 Binding. . . . . . . . . . . . . . . . . . . . . . . . . 3 3 Intracellular Processing - Cleavage and Reduction . . . . . . 4 3. 1 Cytosolic Activity . . . . . . . . . . . . . . . . 5 4 Immunotoxin Design and Testing. 6 5 Conclusion. . 8 References. . . . . 8 1 Introduction While various treatment approaches for cancer include reversal of the transformed phenotype, stimulation of immune responses, inhibition of metastatic spread and deprivation of key nutrients, the goal of immunotoxin treatment is the direct killing of malignant cells. Because they are enzymatic proteins that act catalytically to kill cells, bacterial and plant toxins are often employed as the cell-killing component of immunotoxins. Here we provide background information into the structure-func tion relationships of toxins and discuss how they can be combined with cell-binding antibodies or other ligands to generate immunotoxins. Bacterial and plant toxins (e. g. , diphtheria toxin, Pseudomonas exotoxin and ricin) are among the most toxic substances known. However, because they bind to cell surface receptors that are present on most normal cells, unmodified toxins are generally useless as anti-cancer agents. To convert toxins into more selective agents, their binding domains are either eliminated or disabled and replaceq with cell binding antibodies that are tumor-selective.

Resistance to Immunotoxins in Cancer Therapy

Resistance to Immunotoxins in Cancer Therapy PDF Author: Rama Shanker Verma
Publisher: Springer
ISBN: 3319172751
Category : Medical
Languages : en
Pages : 259

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Book Description
This book will be a guide to understanding resistance against targeted therapeutic approaches for cancer using immunotoxins. It contains a detailed review of the history and development of targeted therapy. As well, it includes an in-depth description of the molecular and cellular mechanisms involved in cancer resistance and several novel methods to overcome resistance. Each chapter discusses different aspects of resistance and covers all the factors that may contribute to resistance in cancer cells. Finally, this volume highlights the recent findings and advances associated with tackling cancer resistance.

Immunotoxin Methods and Protocols

Immunotoxin Methods and Protocols PDF Author: Walter A. Hall
Publisher: Springer Science & Business Media
ISBN: 1592591140
Category : Medical
Languages : en
Pages : 305

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Book Description
Immunotoxins represent a new class of human therapeutics that have widespread applications and a potential that has not yet been fully recognized since they were first conceived of by Paul Ehrlich in 1906. The majority of advances in the development and implementation of immunotoxins has occurred over the last 20 years. The reasons for this use of immunotoxins in basic science and clinical research are the powerful concurrent advances in genetic engineering and receptor physiology. Recombinant technology has allowed investigators to produce sufficient quantities of a homogeneous c- pound that allows clinical trials to be performed. The identification of specific receptors on malignant cell types has enabled scientists to generate immunotoxins that have had positive results in clinical trials. As more cellular targets are identified in coming years, additional trials will be conducted in different disease states affecting still larger patient populations. Modulation of the immune system to decrease the humoral response to immunotoxins may improve their overall efficacy. As increasingly more effective compounds are generated, it will be necessary to decrease the local and systemic toxicity - sociated with these agents, and methods for doing so are presently being - veloped. The work presented in Immunotoxin Methods and Protocols focuses on three specific areas of immunotoxin investigation that are being conducted by experts throughout the world. The first section describes the construction and development of a variety of immunotoxins.

Translational Immunotherapy of Brain Tumors

Translational Immunotherapy of Brain Tumors PDF Author: John H. Sampson
Publisher: Academic Press
ISBN: 0128026251
Category : Science
Languages : en
Pages : 406

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Book Description
Translational Immunotherapy of Brain Tumors gives researchers and practitioners an up-to-date and comprehensive overview of the field. Chapters include adoptive immunotherapy, immunosuppression, CAR therapy of brain tumors, and dendritic cell therapy for brain tumors. Very few agents have been shown to be efficacious in the treatment of malignant gliomas. Recently, there have been a number of studies demonstrating the potential success of immunotherapy for brain tumors. Immunotherapeutics are becoming the most frequent drugs to be used in cancer therapy. These new breakthroughs, now approved by the FDA, are a part of multiple phase III international trials and ongoing research in malignant glioma, meaning that the information in this cutting-edge book will be of great importance to practitioners and researchers alike. Comprehensive overview, providing an update on immunology, translational immunotherapy, and clinical trials relating to malignant gliomas Edited by a prominent neurosurgeon with contributions by leading researchers in the field Ideal resource for researchers and practitioners interested in learning about mechanisms that use the immune system to treat brain tumors

Treatment of Bone and Soft Tissue Sarcomas

Treatment of Bone and Soft Tissue Sarcomas PDF Author: Per-Ulf Tunn
Publisher: Springer Science & Business Media
ISBN: 3540779604
Category : Medical
Languages : en
Pages : 372

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Book Description
Bone and soft tissue sarcomas represent only about 2% of all malignancies; however, their treatment – with the goal of curing the patient while preserving the functionality of the affected body part – can, unlike other malignancies, only be successful with therapy concepts devised by interdisciplinary teams. This volume provides an extensive up-to-date overview of the specific diagnostics and current treatment standards of these rare entities, presenting the various limb-sparing modalities for patients with bone and soft tissue sarcomas with special regard to innovative reconstructive options. The evaluation of quality of life based on validated scores and the individual methods of coping with the illness through creative artistic projects are also acknowledged and integrated in the whole concept.

Corynebacterium Diphtheriae and Related Toxigenic Species

Corynebacterium Diphtheriae and Related Toxigenic Species PDF Author: Andreas Burkovski
Publisher:
ISBN: 9789400776258
Category :
Languages : en
Pages : 312

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Book Description


Toxins and Cancer Therapy

Toxins and Cancer Therapy PDF Author: Adam E. Snook
Publisher: MDPI
ISBN: 3036501908
Category : Science
Languages : en
Pages : 104

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Book Description
Cancer has been a patient-specific and difficult-to-treat disease for decades, resulting in more deaths since 1900 than all other diseases except cardiovascular diseases. As societies around the world continue to shift towards an aging population, the social and economic burden created by cancer will only rise in the coming decades, necessitating continued improvement in our cancer therapies. Remarkably, in the late 1800s, bone surgeon William Coley serendipitously discovered that bacteria could be administered to patients as an effective (and sometimes toxic) form of cancer therapy known as "Coley's Toxins". His discoveries unknowingly led to two fields of cancer therapy that have been in development for decades and are now leading to significant improvements in therapy for cancer patients: immune-based and toxin-based therapies for cancer. Articles included here discuss the discoveries that emerged from Coley's Toxins that enable us to harness the immune system and microbial toxins to combat cancers, as oncology shifts from a field dominated by chemotherapy for most of the 20th century to biologic therapies that will dominate the 21st century.

Novel Immunotherapeutic Approaches to the Treatment of Cancer

Novel Immunotherapeutic Approaches to the Treatment of Cancer PDF Author: Paul D. Rennert
Publisher: Springer
ISBN: 9783319806624
Category : Medical
Languages : en
Pages : 276

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Book Description
Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered. The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.