Jeffrey Wang, Wei-Chiang Shen, Jennica L. Zaro's Antibody-Drug Conjugates: The 21st Century Magic Bullets for PDF

By Jeffrey Wang, Wei-Chiang Shen, Jennica L. Zaro

ISBN-10: 3319130803

ISBN-13: 9783319130804

ISBN-10: 3319130811

ISBN-13: 9783319130811

This authoritative quantity presents a holistic photo of antibody-drug conjugates (ADCs). Fourteen complete chapters are divided into six sections together with an creation to ADCs, the ADC build, improvement concerns, panorama, IP and pharmacoeconomics, case stories, and the way forward for the sphere. The publication examines every thing from the choice of the antibody, the drug, and the linker to a dialogue of developmental matters equivalent to formulations, bio-analysis, pharmacokinetic-pharmacodynamic relationships, and toxicological and regulatory demanding situations. It additionally explores pharmacoecomonics and highbrow houses, together with lately issued patents and the price research of drug treatment. Case stories are provided for the 3 ADCs that experience got FDA approval: gemtuzumab ozogamicin (Mylotarg®), Brentuximab vedotin (Adcetris®), and ado-trastuzumab emtansine (Kadcyla®), in addition to an ADC in late-stage scientific trials, glembatumumab vedotin (CDX-011). ultimately, the quantity provides a point of view by means of the editors at the destiny instructions of ADC improvement and scientific functions. Antibody-Drug Conjugates is a pragmatic and systematic source for scientists, professors, and scholars drawn to increasing their wisdom of state of the art examine during this fascinating field.

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Additional resources for Antibody-Drug Conjugates: The 21st Century Magic Bullets for Cancer

Example text

A Screening for internalization using fluorescencebased approaches, In fluorescence-based assays, target cells can be bound to antibodies at 4 ℃, warmed to 37 ℃ to allow for internalization, washed to remove extracellular antibodies, and fixed and stained with fluorescent secondary reagents to visualize internalized antibodies. Alternatively (not shown), antibodies directly conjugated to fluorophores can be used for internalization, and secondary antibodies omitted. Internalization can be measured qualitatively or quantitatively by microscopy or flow cytometry.

The source for antibodies can be immunized animals, cancer patients, or phage display libraries with antibodies from naïve or tumor-exposed sources using a range of techniques, from conventional hybridoma generation or phage panning to B cell sorting and V gene isolation from immune sources or selection of phage binding to or internalizing in cells expressing the target. Once lead antibodies are cloned and selected, the antibodies can be recombinantly expressed and validated. 2 Selection and Validation of Tumor-Associated Targets Using Omics Approaches Most strategies used for the identification of targets amenable to the ADC approach resemble strategies used to identify tumor-associated cell-surface antigens for other oncology biotherapeutic approaches, though with a few notable differences.

3 Engineering Fc-Mediated Interactions Fc-mediated effector function accounts for most of the in vivo efficacy imparted by unconjugated mAbs in cancer therapy. However, the role of Fc effector function in inhibition of tumor growth by an ADC in the clinic remains unclear. Several strategies have been employed to enhance immune-mediated effector functions of unconjugated mAbs, including afucosylation as well as mutations in the antibody-Fc region, both of which can enhance FcγR binding and amplify antibody-dependent cell-mediated cytotoxicity (ADCC).

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Antibody-Drug Conjugates: The 21st Century Magic Bullets for Cancer by Jeffrey Wang, Wei-Chiang Shen, Jennica L. Zaro

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