Development of Anti-Idiotype Monoclonal Antibodies for the Treatment of Breast Cancer


Book Description

For the development of HER2/neu mimicking anti-idiotype antibodies (Ab2s), groups of female BALD/c mice were immunized with three sets of monoclonal antibodies (Ab1), designated 520C9, 741F8 and 454C11, directed at distinct antigenic determinants of HER2/neu. Hybridomas were generated from each treatment group and one, stable Ab2 producing hybrid each of 520C9 and 741F8 were obtained, and cloned twice by limiting dilution. The isotypes of 520C9 and 741F8 Ab2's were IgG1k by ELISA. 520C9 and 741F8 Ab2 cells were used to produce mouse ascites and the Ab2 purified by affinity chromatography and confirmed by SDS-PAGE. A competitive binding assay using Ab2, Ab1 and the human breast cancer cell line SK-BR-3 (which express HER2/neu on their cell surface), showed that 50mu1 of each of 520C9 and 741F8 Ab2 containing supernatants inhibited the binding of Ab1 to SK-BR-3 cells by tilde 80%. The specificity binding study showed that the binding of 741F8 Ab2 was to those antibodies directed against HER/2neu. A competitive binding assay using 741F8 Ab2, Ab1 and SK-BR-3 cells showed that 10ng of purified 741F8 Ab2 inhibited the binding of Ab1 to SK-BR-3 cells by tilde 50%. Polyclonal anti-anti-idiotype antibodies (Ab3), were generated in rabbits using either purified 520C9 Ab2 or 741F8 Ab2. The Ab3 reacted with HER2/neu positive tumor cells suggesting the presence of anti-tumor (Ab1') antibodies.




Anti-idiotype antibodies in cancer treatment


Book Description

Actively induced immunotherapy is one of the most promising fields in cancer research and numerous approaches are being studied to design effective cancer vaccines. Among the treatment strategies to develop an effective immune response against tumor associated antigens is the use of anti idiotype (Ab2) mAb as antigen surrogates. Several studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against tumors of different origin. In fact, anti-idiotypic mAbs have been used successfully in cancer therapeutics to overcome the poor immunogenicity of some tumor-associated antigens, in particular those of non-protein origin. In some clinical trials, including patients with different tumors, anti-Id specific humoral and/or cellular responses following immunization were associated with improved clinical outcome. This number of Frontiers will be dedicated to anti- idiotypic antibodies and their use in cancer treatment. Different article types will be considered: original contributions, case reports, methods, hypothesis and theory, reviews, historical, etc.




Monoclonal Antibody Therapy of Human Cancer


Book Description

KENNETH A. FOON and ALTON C. MORGAN, JR. Passive immunotherapy using heteroantisera for the treatment of cancer in animals and humans has been studied for over 50 years. Attempts have been made to treat animal tumors with sera from immunized syngeneic, allogeneic, or xenogeneic animals. A number of studies of passive immunotherapy using heterologous antisera in humans have also been performed. These studies have generally been attempted in patients with large tumor burdens, and as would be expected, results have been transient at best. A wide variety of solid tumors as well as leukemias and lym phomas have been treated with antisera raised in sheep, horses, rabbits, and goats. Problems such as anaphylaxis, serum sick ness, and severe cytopenias have been encountered with these antisera. There are a number of potential mechanisms by which unconju gated antibodies might be cytotoxic to tumor cells. Antibodies bound to the cell surface membrane of tumor cells may lead to cell lysis by complement-dependent or antibody-dependent cellu lar cytotoxicity. Circulating tumor cells bound by antibody may be more susceptible to phagocytosis by the reticuloendothelial system. Antibody bound to the cell surface membrane of tumor cells may enhance immunogenicity of the tumor cell leading to activation of the host's immune system.




Safety of Biologics Therapy


Book Description

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.




Antigen and Antibody Molecular Engineering in Breast Cancer Diagnosis and Treatment


Book Description

Today, advances in the area of immunology and breast cancer are made at an increasing rate, yielding an amount of information that can become unwieldy. The opportunity for scientists in this area of research to gather together to exchange results and working hypotheses represents, in my belief, a very attractive proposition. With this in mind, these workshops have been convened with two year intervals for the last ten years. In each of them, selected topics have been highlighted. The present workshop underscores the large advancements made in the molecular biology of both breast cancer associated antigens and their corresponding antibodies. Understanding the genetic information for the expression of these antigens has been recently advanced leading to preparation of molecularly engineered reagents for use in vaccination, serum assays, and immunizations for novel antibody production. In the anti-breast cancer antibody field the availability of molecular engineering approaches to humanize murine antibodies has induced intense interest in the creation of less immunogenic antibody forms that are now available for clinical testing. Clinical studies using anti-breast murine antibody continue to be carried out and are presented at this meeting establishing a base line for safety and efficaciousness in imaging and immunotherapy that it is hoped will be superseded by the humanized forms. Basic immunology and immunochemistry studies in breast cancer are also included in this workshop that demonstrate the fast pace at which this research is advancing in many laboratories worldwide.




Idiotypes in Medicine: Autoimmunity, Infection and Cancer


Book Description

This is the most comprehensive review of the idiotypic network available. All the current knowledge of idiotypes of the various antibodies is incorporated in this volume. The pathogenic role of idiotypes in autoimmunity and cancer is reviewed in depth. The therapeutic part focusses on harnessing anti-idiotypes for treating autoimmunological disorders, and on the employment of idiotypes for vaccines in cancer and infectious diseases, as well as explaining the manipulation of the idiotypic network in autoimmunity and cancer idiotypes and vaccines.




Therapeutic Antibodies


Book Description

This essential work, edited by two researchers at London’s famous Queen Mary’s medical school targets one of the most important areas in medical development today. These days, antibody therapeutics are the treatment of choice for several autoimmune and oncological conditions. They are, indeed, becoming the molecules of choice for further combination therapies and cell engineering. In this timely work, a slew of expert in the field of drug development summarize all the current developments and clinical successes.




Monoclonal Antibodies and Breast Cancer


Book Description

Breast cancer, being a disease with very high prevalence in the female population, has permanently attracted the attention of biologists, biochemists, pathologists, surgeons, and oncologists. In the U.S. alone approximately 120,000 new cases are diagnosed and 37,000 deaths a year are recorded as an outcome. Early diagnosis, clear cut prognosis and the hope of new therapeutic approaches has spurred the enthusiasm of researchers, who with the advent of newer methodologies, tried to employ it in different approaches to the breast cancer patient. In spite of the efforts devoted towards the creation of new approaches, reagents and procedures taking advantage of special characteristics of the breast tissue were slow to come. In general, most diagnostic and prognostic techniques were those shared and applied to other carcinomas. In the early seventies we discovered the first sets of antigens associated with breast epithelial tissue both in the mouse and the human. The recognition of such group of molecules, present in the milk fat globule membrane, gave impetus to several studies in these areas. These mammary cell surface antigens proved useful in several diagnostic approaches such as radioimaging, histochemical and serum assay procedures. However, the apparently inherent limitations of polyclonal antibodies reduced the impact of these novel approaches.







Breast Cancer Immunodiagnosis and Immunotherapy


Book Description

The convening of the 3rd International Workshop on Monoclonal Antibodies and Breast Cancer had the character of a self-search exercise. After almost a decade of research in the basic and applied aspects of the use of serological means to diagnose and possibly treat breast cancer several milestones have been reached. Among them a clear understanding of immunopathological use and limitations of monoclonal antibodies against breast epithelium, the complete development and clinical use of immunoassays for circulating breast epithelial antigens, the striking advances in the diagnostic use of monoclonal antibodies to estrogen and progesterone receptor proteins and the first communications on proposed immunotherapeutic use of different conjugates of anti-breast antibodies. New areas of investigation have developed in our field, some which are reaching a full blossom while others are still facing obstacles and at times a re-definition of their goals and objectives. These meetings have acted in a way as a clearing house and have permitted their attendees to derive predictions that have helped shape future research and fine-tune objectives. But above all, the re-evaluation of past research at these Workshops and the renewed excitement brought to them by new information has helped generate a momentum and enthusiasm that assures for the future large scientific gains.