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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.

Farmacologie [Immuno] --- Immunofarmacologie --- Immunopharmacologie --- Immunopharmacology --- Pharmacoimmunology --- Pharmacologie [Immuno] --- Immunotoxins --- Diphtheria toxin --- Ricin --- therapeutic use --- pharmacology --- therapeutic use. --- pharmacology. --- Therapeutic use. --- Pharmacology. --- Antibody-toxin conjugates --- Therapeutic use --- Immunology. --- Cancer research. --- Hematology. --- Cancer Research. --- Pharmacology/Toxicology. --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemicals --- Chemotherapy --- Drugs --- Pharmacy --- Haematology --- Internal medicine --- Blood --- Cancer research --- Immunobiology --- Life sciences --- Serology --- Physiological effect --- Diseases --- Antibody-toxin conjugates. --- Conjugates, Antibody-toxin --- Immunoconjugates --- Immunoglobulin-toxin conjugates --- Toxin-antibody conjugates --- Toxin-immunoglobulin conjugates --- Bioconjugates --- Immunotoxicology --- Toxins

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This volume is 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.

Biomedicine. --- Cancer Research. --- Drug Resistance. --- Pharmacology/Toxicology. --- Medicine. --- Oncology. --- Drug interactions. --- Toxicology. --- Médecine --- Cancérologie --- Médicaments --- Toxicologie --- Interaction --- Medicine --- Health & Biological Sciences --- Oncology --- Antibody-toxin conjugates. --- Cancer --- Treatment. --- Cancer therapy --- Cancer treatment --- Conjugates, Antibody-toxin --- Immunoconjugates --- Immunoglobulin-toxin conjugates --- Immunotoxins --- Toxin-antibody conjugates --- Toxin-immunoglobulin conjugates --- Therapy --- Cancer research. --- Drug resistance. --- Pharmacology. --- Bioconjugates --- Immunopharmacology --- Immunotoxicology --- Toxins --- Chemicals --- Pharmacology --- Poisoning --- Poisons --- Interactions, Drug --- Drugs --- Tumors --- Toxicology --- Side effects --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemotherapy --- Pharmacy --- Resistance to drugs --- Cancer research --- Physiological effect

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The concept of delivering ‘magic bullets’ to treat diseases was first proposed by Paul Erlich in the early 1900’s.  The realization of this concept for the treatment of cancer occurred in the late 1990’s with the approval of monoclonal antibody therapies.  The use of monoclonal antibodies conjugated (linked) to potent cytotoxic agents (antibody-drug conjugates, ADCs) for specifically delivering cytotoxics to cancer cells was an obvious extension of antibody-based therapy.  ADCs have been under intense investigation for several decades; progress, however, has been limited due to toxicity or lack of improved efficacy compared to unconjugated cytotoxics.  More recently, linker technology and target selection have advanced such that several ADCs and immunotoxins are undergoing clinical testing or are approved for use.  This important volume gives the latest and most comprehensive information on the topic, describing different types of ADCs and immunotoxins for both hematologic and solid malignancies. Finally, the volume highlights the promise that this technology holds for diverse types of human cancer.

Antibodies. --- Antibody-drug conjugates. --- Immunotoxins -- Therapeutic use. --- Antibody-drug conjugates --- Antibody-toxin conjugates --- Diseases --- Pharmaceutical Preparations --- Immunoconjugates --- Immunoglobulins --- Therapeutics --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Immunoproteins --- Chemicals and Drugs --- Blood Proteins --- Proteins --- Amino Acids, Peptides, and Proteins --- Immunotoxins --- Neoplasms --- Drug Therapy --- Antibodies --- Drug Combinations --- Medicine --- Health & Biological Sciences --- Oncology --- Antibody-toxin conjugates. --- Conjugates, Antibody-toxin --- Immunoglobulin-toxin conjugates --- Toxin-antibody conjugates --- Toxin-immunoglobulin conjugates --- Conjugates, Antibody-drug --- Drug-antibody conjugates --- Drug immunoconjugates --- Drug-immunoglobulin conjugates --- Immunoconjugates, Drug --- Immunoglobulin-drug conjugates --- Medicine. --- Cancer research. --- Biomedicine. --- Cancer Research. --- Biomedicine general. --- Immune globulins --- Immune serum globulin --- Blood proteins --- Globulins --- Plasma cells --- Antibody diversity --- Antigens --- Bacterial immunoglobulin-binding proteins --- Cancer research --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Bioconjugates --- Immunopharmacology --- Immunotoxicology --- Toxins --- Drugs --- Dosage forms --- Oncology. --- Monoclonal antibodies. --- Antibodies, Monoclonal --- Monoclonal immunoglobulins --- Molecular cloning --- Tumors --- Health Workforce --- Biomedicine, general.