Monoclonal Antibodies In Cancer

This represents the third volume in a series on cancer markers pub lished by the Humana Press. The first volume, published in 1980, stressed the relationship of development and cancer as reflected in the production of markers by cancer that are also produced by normal cells during fetal development. The concept that cancer represents a problem of differentiation was introduced by Barry Pierce in describing differenti ation of teratocarcinomas. Highlighted were lymphocyte markers, alphafetoprotein, carcinoembryonic antigen, ectopic hormones, enzymes and isozymes, pregnancy proteins, and fibronectin. The second volume, published in 1982 and coedited with Britta Wahren, focused on the diagnostic use of oncological markers in human cancers, which were systematically treated on an organ by organ basis. At that time, the application of monoclonal antibodies to the identification of cancer markers was still in a very preliminary stage. A general introduc tion to monoclonal antibodies to human tumor antigens was given there by William Raschke, and other authors included coverage of those mark ers then detectable by monoclonal antibodies in their chapters.

Drug-Induced Liver Injury, Volume 85, the newest volume in the Advances in Pharmacology series, presents a variety of chapters from the best authors in the field. Chapters in this new release include Cell death mechanisms in DILI, Mitochondria in DILI, Primary hepatocytes and their cultures for the testing of drug-induced liver injury, MetaHeps an alternate approach to identify IDILI, Autophagy and DILI, Biomarkers and DILI, Regeneration and DILI, Drug-induced liver injury in obesity and nonalcoholic fatty liver disease, Mechanisms of Idiosyncratic Drug-Induced Liver Injury, the Evaluation and Treatment of Acetaminophen Toxicity, and much more. Includes the authority and expertise of leading contributors in pharmacology Presents the latest release in the Advances in Pharmacology series

The book broadly deals with therapeutic monoclonal antibodies (mAbs) and various relevant topics, including different antibody formats such as Antibody-Drug Conjugates (ADC), bispecifics, nanoparticle-based mAbs and HER2+ cancers, immune checkpoint inhibitors and other closely related topics. Each paper was written by leading active research groups in their fields both from academia and industry. The book should be of interest to those scientists and researchers who develop or use biologics, biotherapeutics, biosimilars and biobetters in cancer treatment.

A comprehensive account of cancer immunity and immunotherapy, examining recent results, current areas of interest and the specific issues that are affecting the research and development of vaccines. It provides insight into how these problems may be overcome as viewed by leaders in the field.

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.

The American Anti-Vivisection Society (AAVS) petitioned the National Institutes of Health (NIH) on April 23, 1997, to prohibit the use of animals in the production of mAb. On September 18, 1997, NIH declined to prohibit the use of mice in mAb production, stating that "the ascites method of mAb production is scientifically appropriate for some research projects and cannot be replaced." On March 26, 1998, AAVS submitted a second petition, stating that "NIH failed to provide valid scientific reasons for not supporting a proposed ban." The office of the NIH director asked the National Research Council to conduct a study of methods of producing mAb. In response to that request, the Research Council appointed the Committee on Methods of Producing Monoclonal Antibodies, to act on behalf of the Institute for Laboratory Animal Research of the Commission on Life Sciences, to conduct the study. The 11 expert members of the committee had extensive experience in biomedical research, laboratory animal medicine, animal welfare, pain research, and patient advocacy (Appendix B). The committee was asked to determine whether there was a scientific necessity for the mouse ascites method; if so, whether the method caused pain or distress; and, if so, what could be done to minimize the pain or distress. The committee was also asked to comment on available in vitro methods; to suggest what acceptable scientific rationale, if any, there was for using the mouse ascites method; and to identify regulatory requirements for the continued use of the mouse ascites method. The committee held an open data-gathering meeting during which its members summarized data bearing on those questions. A 1-day workshop (Appendix A) was attended by 34 participants, 14 of whom made formal presentations. A second meeting was held to finalize the report. The present report was written on the basis of information in the literature and information presented at the meeting and the workshop.

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.