By Jeffrey Wang, Wei-Chiang Shen, Jennica L. Zaro
This authoritative quantity presents a holistic photo of antibody-drug conjugates (ADCs). Fourteen finished chapters are divided into six sections together with an advent to ADCs, the ADC build, improvement matters, panorama, IP and pharmacoeconomics, case reviews, and the way forward for the sphere. The ebook examines every thing from the choice of the antibody, the drug, and the linker to a dialogue of developmental matters reminiscent of 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 associated fee research of drug remedy. Case stories are awarded 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 medical trials, glembatumumab vedotin (CDX-011). eventually, the amount offers a point of view via the editors at the destiny instructions of ADC improvement and medical functions. Antibody-Drug Conjugates is a realistic and systematic source for scientists, professors, and scholars drawn to increasing their wisdom of state-of-the-art examine during this interesting field.
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Additional resources for Antibody-Drug Conjugates: The 21st Century Magic Bullets for Cancer
2012). In a separate study, this technology was also used to produce an anti-5T4 and an anti-HER2 site-specific ADC, containing two monomethyl auristatin D (MMAD) payloads per antibody (Sapra et al. 2013; Tian et al. 2014). These particular site-specific ADCs (NDCs) also possessed improved in vitro cytoxicity, superior in vivo efficacy, increased PK stability relative to the conventional conjugates, and were well tolerated in preclinical toxicology studies (Sapra et al. 2013; Tian et al. 2014).
Alternatively, liposomes can be loaded with a cytotoxin or immunotoxin in order to measure the ability of the antibody to confer target-mediated killing (An et al. 2008; Harper et al. 2013). However, the high valency of conjugated liposomes may result in internalization and trafficking properties that differ significantly from those of conventional IgG. 2 Screening for Intracellular Toxin Delivery The ability of antibodies to internalize and deliver toxins to the cell type of interest can also be measured directly, and increasing numbers of methods are becoming available to allow rapid screening of hundreds to thousands of antibodies.
Cancer Res 61(12):4750–4755 Akahori Y, Kurosawa G, Sumitomo M, Morita M, Muramatsu C, Eguchi K, Tanaka M, Suzuki K, Sugiura M, Iba Y, Sugioka A, Kurosawa Y (2009) Isolation of antigen/antibody complexes through organic solvent (ICOS) method.