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Systemic Radiotherapy with Monoclonal Antibodies

Systemic Radiotherapy with Monoclonal Antibodies
Author: Marie-Luise Sautter-Bihl
Publisher: Springer Science & Business Media
Total Pages: 200
Release: 2012-12-06
Genre: Medical
ISBN: 3642799523
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Almost a century ago Paul Ehrlich introduced the "magic bullet" concept of targeting therapeutic agents to specific tissues in order to reduce systemic toxicity. Due to the advances in hybridoma technology in the 1980s, monoclonal antibodies (MAbs) with their exquisite affinity to tumor antigens have become powerful tools in the treatment of cancer, especially when linked to therapeutic agents such as radionuclides, drugs, toxins, or enzymes. It can now be expected that such agents will lead to new cancer treatments with high therapeutic success rates. However, there are major problems in developing this therapeutic concept to a routine treatment modality. This is partly due to factors such as heterogenous distribution of tumor antigens, insufficient blood supply of tumors, high interstitial pressure, and the large interstitial space that antibodies have to traverse. This book is focused on the development in radio immunotherapy (RIT) using radio labeled monoclonal antibodies as tumoritoxic agents. This area of research has attracted the interest of clinicians and scientists from many different disciplines. It is now clear that the full potential of RIT can only be realized through the concerted efforts of laboratory scientists (molecular biologists, cell physiologists, chemists, radiation physicists, and biologists) and cancer clinicians in nuclear medicine, radiooncology, and internal oncology.

Radiolabeled Monoclonal Antibodies for Imaging and Therapy

Radiolabeled Monoclonal Antibodies for Imaging and Therapy
Author: Suresh C. Srivastava
Publisher: Springer Science & Business Media
Total Pages: 851
Release: 2013-03-14
Genre: Medical
ISBN: 1468455389
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The advent of hybridoma technology leading to the successful produc tion of monoclonal antibodies against a variety of tumor-associated antigens has, during the last decade, provided a very powerful tool for research and clinical investigations. These highly specific reagents have essentially replaced the polysera of the earlier days. The successful demonstration of the many wide ranging capabilities of the monoclonal antibody technique has already begun to exert an enormous impact on diverse areas of research in basic science and medicine. In particular, the potential of monoclonal antibodies to serve as carriers for selective targeting of radionuclides to tumors for diagnosis or therapy, has stimulated an intense surge of research interest and even revived hopes of realizing Ehrlich's concept of the "magic bullet". Indeed, the technology appears to be on the threshold of a revolution in diagnosing and treating malignant disease. Much work remains to be done, however, and even though the progress has been impressive, results to date have shown only moderate success. There is no question that the limited success we have achieved thus far is merely a prelude to the many more exciting developments yet to come.

Safety of Biologics Therapy

Safety of Biologics Therapy
Author: Brian A. Baldo
Publisher: Springer
Total Pages: 623
Release: 2016-08-12
Genre: Medical
ISBN: 3319304720
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This long overdue title provides a comprehensive, up-to-date, state-of-the art review of approved biologic therapies, with coverage of mechanisms of action, Indications for therapy, immunogenicity and a detailed examination of adverse effects and safety of the many and diverse therapeutic agents presented in a total of 13 chapters. It is predicted that by 2016, biologics will make up half of the world's 20 top-selling drugs and by 2018, biologic medicine sales will account for almost half of the world's 100 biggest selling drugs. Recombinant proteins dominate the growing list of the more than 200 approved biotherapeutic agents with targeted antibodies, fusion proteins and receptors; cytokines; hormones; enzymes; proteins involved in blood-clotting, homeostasis and thrombosis; vaccines; botulinum neurotoxins; and, more recently, biosimilar preparations, comprising the majority of approved biologics. Written with clinicians, other health care professionals, and researchers in mind, Safety of Biologics Therapy examines, in a single volume, the full range of issues surrounding the safety of approved biologic therapies. A good understanding of the risks and safety issues of modern biologics therapy is increasingly being demanded of all those connected with their development, handling, prescribing, administration and subsequent patient management. In addition to being of great value to clinicians in all branches of medicine, and to nurses, pharmacists and researchers, this book will prove invaluable for students taking undergraduate and graduate courses in the above disciplines and in the biomedical sciences.

Cancer Therapy

Cancer Therapy
Author: Hans G. Beger
Publisher: Springer Science & Business Media
Total Pages: 347
Release: 2012-12-06
Genre: Medical
ISBN: 3642737218
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A variety of new cancer therapy modalities are discussed and evaluated in this book. It aims to demonstrate that the combination of classical chemo- and radiotherapy with new approaches in the field of immunotherapy can result in an improved treatment modality. Immunotherapy in this context consists of therapy with monoclonal antibodies, hematopoietic growth factors and other lymphokines. Results of early clinical trials with IL-2, GM-CSF and monoclonal antibodies against gastrointestinal tumors and melanoma are included. The progress in regional chemotherapy strategies, for example of the liver, is shown. In addition, the development of new chemotherapeutic agents with a different mode of action as well as better tolerability is presented. The use of hormones, such as LH-RH agonists, allows hormone-dependent tumors such as prostatic and breast cancer to be treated without strong adverse reactions. These recent findings give the reader insight into exciting therapeutic directions made possible by such combined, rather than single, modalities.

Targeted Radionuclide Therapy

Targeted Radionuclide Therapy
Author: Tod W. Speer
Publisher: Lippincott Williams & Wilkins
Total Pages: 564
Release: 2012-03-28
Genre: Medical
ISBN: 1451153260
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Radioimmunotherapy, also known as systemic targeted radiation therapy, uses antibodies, antibody fragments, or compounds as carriers to guide radiation to the targets. It is a topic rapidly increasing in importance and success in treatment of cancer patients. This book represents a comprehensive amalgamation of the radiation physics, chemistry, radiobiology, tumor models, and clinical data for targeted radionuclide therapy. It outlines the current challenges and provides a glimpse at future directions. With significant advances in cell biology and molecular engineering, many targeting constructs are now available that will safely deliver these highly cytotoxic radionuclides in a targeted fashion. A companion website includes the full text and an image bank.

Cancer Therapy with Radiolabeled Antibodies

Cancer Therapy with Radiolabeled Antibodies
Author: David M. Goldenberg
Publisher: CRC Press
Total Pages: 405
Release: 2018-01-18
Genre: Law
ISBN: 1351087304
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Cancer Therapy with Radiolabeled Antibodies explores the most current experimental and clinical advances in the newly emerging field of cancer radioimmunotherapy (RAIT). Providing a multidisciplinary and international context, some of the world's leading experts examine the problems and prospects of RAIT from radiation, immunological, chemical, physical, physiological, and clinical perspectives with both overviews and original research. Discussions cover the up-to-date clinical results in the RAIT of ovarian, breast, colorectal, and brain cancers, as well as the current status of RAIT in the management of B cell lymphomas. Radiobiology, dosimetry, radiochemistry, targeting biology in experimental models, clinical experiences in hematopoietic and solid tumors, and new approaches to improve cancer radioimmunotherapy are also discussed. In addition, new dosimetry concepts, new labeling methods, new concepts of antibody pharmacokinetics, and new methods to enhance selective cancer radioimmunotherapy are included.

Using Low-dose Radiation Therapy to Propagate Systemic Response to in Situ Vaccines

Using Low-dose Radiation Therapy to Propagate Systemic Response to in Situ Vaccines
Author: Peter Michael Carlson
Publisher:
Total Pages: 233
Release: 2020
Genre:
ISBN:
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Despite substantial improvement in clinical cancer care, disease progression still occurs. The Sondel lab has developed a combination in situ vaccine (ISV) immunotherapy approach consisting of 12Gy local external beam radiation (RT) and intratumoral injections of hu14.18-IL2 immunocytokine (IC, a fusion of an anti-GD2 monoclonal antibody and IL-2) for treatment of GD2+ tumors. This ISV approach can render up to 70% of mice bearing a single B78 melanoma flank tumor disease-free, with tumor-specific systemic memory, but is insufficient to control distant, untreated tumors in models of multiple B78 implanted tumors. The goal of this thesis was to characterize the efficacy of using low-dose radiation (both RT and molecular targeted radionuclide therapy [TRT, [90]Y-NM600]) delivered to all sites of disease in enabling a systemic antitumor response following RT/IC ISV. Many shared resource cytometry facilities do not permit analysis of radioactive tissue for safety and radioactive waste disposal concerns. By investigating introduction of a cryopreservation step in the flow cytometry workflow, I demonstrated that cryopreservation of dissociated tumor and spleen cells after all staining and fixation gave results most concordant with non-cryopreserved cells, which allowed for analyses of radioactive TRT-treated tumors. In addition, I characterized a discrepancy in treatment outcome among mice implanted with B78 tumors treated with ISV. I determined that tumors implanted subcutaneously display a 'fixed' phenotype and are less likely to respond to RT/IC ISV. Conversely, tumors implanted intradermally are 'mobile' in phenotype and respond well to RT/IC ISV. After controlling for implantation depth, I determined that RT/IC ISV delivered to a primary B78 melanoma combined with either RT or [90]Y-NM600 TRT to secondary tumors resulted in greater antitumor effect compared to either RT/IC alone or radiation alone, as demonstrated by overall survival, and analysis of tumor growth rates. These data suggest that additional radiation to all disease sites is indeed capable of improving response to RT/IC ISV at distant sites. Ongoing studies are using flow cytometry and cytokine quantification to characterize the nature of the immune response to ISV at distant tumors, with and without additional radiation.