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The covalent conjugation of potent cytotoxic agents to monoclonal antibodies, known as antibody-drug conjugates (ADCs) is a powerful approach in the field of targeted treatment of cancer. Clearly, both monoclonal antibody and cytotoxic payload are crucial elements in determining the clinical value of an ADC and have receive ample attention. However, the structural element connecting the two –the chemical linker– also plays an essential role in mode-of-action, efficacy, pharmacokinetics and safety profile of an ADC, but is often underappreciated in considerations of ADC design.Chemical Linkers in Antibody–Drug Conjugates aims to shine a detailed light on the various key attributes of chemical linkers in ADCs, for drug-to-antibody ratio, for stability, for release mechanism of payload, for pharmacokinetics, for stability determination, and for efficacy and safety. Ideal for postgraduate students and active researchers in drug discovery and development, this book provides a comprehensive description of linkers used in ADCs (clinical and late preclinical), insight into key quality attributes of linkers for ADCs, and aids the reader in understanding the role of linker chemistry and designing new ADCs.
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Drug developers share strategies for next-generation antibody-based cancer therapeuticsCancer immunotherapy has produced two transformative drug classes: bispecific antibodies and antibody-drug conjugates. Trends in Antibody Drug Discovery for Cancer Therapy brings together drug developers from pharmaceutical companies of all sizes to share their experiences developing these therapeutics. Christian Klein, whose Roche team contributed to twenty-four clinical stage bispecific antibodies, offers key insights into successful strategies for anticancer drug development.This book begins with a review of recent therapy developments in biological cancer treatment before examining bispecific antibodies and antibody-drug conjugates through detailed case studies of recently approved therapeutics. An international team of contributors then examine how bispecific antibodies target both cancer and immune cells, and how antibody-drug conjugates deliver cytotoxic payloads directly to tumors. The final section evaluates emerging approaches including antibody-based PROTACs and cytokine mimetics.Readers will also benefit from: Case studies documenting the development pathways of recently approved bispecific antibodies and antibody-drug conjugates from preclinical research through to clinical applicationAnalysis of targeted protein degradation strategies including antibody-based PROTACs and their potential for harnessing this mechanism in cancer therapyExpert evaluation of cytokine mimetics and other forward-looking approaches contributing to the next generation of antibody-based cancer treatmentsInsights from drug developers at both small and large pharmaceutical companies sharing past successes and future development plansDesigned for medicinal chemists, pharmaceutical chemists, and oncologists working in drug discovery and development, this volume addresses the unmet medical need for more efficient cancer therapeutics. Industry professionals will gain actionable insights for developing antibody-based drugs in a field that leads global pharmaceutical markets.