Kenneth J. Olivier Jr., Sara A. Hurvitz's Antibody-Drug Conjugates: Fundamentals, Drug Development, PDF

By Kenneth J. Olivier Jr., Sara A. Hurvitz

ISBN-10: 1119060680

ISBN-13: 9781119060680

Providing useful and confirmed recommendations for antibody-drug conjugate (ADC) drug discovery good fortune in oncology, this e-book is helping readers increase the drug security and healing efficacy of ADCs to kill unique tumor cells.

• Discusses the fundamentals, drug supply options, pharmacology and toxicology, and regulatory approval strategies
• Covers the behavior and layout of oncology medical trials and using ADCs for tumor imaging
• Includes case stories of ADCs in oncology drug development
• Features contributions from highly-regarded specialists at the frontlines of ADC learn and development

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Additional info for Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer

Example text

3). It is possible that these mechanisms can operate in the pre-endosomal and endosomal c­ ompartments 1 Typical Antibody–Drug Conjugates of cells without a strict requirement for lysosomal trafficking, although in the case of proteolytic cleavage, one must design peptide linkers susceptible to the proteases present in such nonlysosomal compartments. ” In other cases, the final active cytotoxic metabolite released intracellularly from the ADC is a derivative of the “parent” cytotoxic compound, which now includes structures and/or functional groups introduced as part of the linker chemistry.

3 mg/kg (squares), which are equivalent to 24 ± 3, 49 ± 2, and 98 ± 4 µg/kg conjugated maytansinoid, respectively. 0 mg/kg (90 µg/kg conjugated maytansinoid). The effect of weekly administration of IMGN853 on the antitumor activity against KB xenograft tumors is shown in (c). 8 mg/kg antibody) on day 6 postinoculation (open triangles), or with multiple injections (qw × 3) on day 7, 14, and 21 postinoculation (solid circles). , Molecular Cancer Therapeutics, 14(7); 1605–1613, copyright 2015, American Association for Cancer Research [22].

The two maytansinoid ADCs show examples of conjugates with either a non-cleavable link created by reaction of the sulfhydryl group of the maytansinoid DM1 with the maleimido group of the linker (thioether bond so formed is shaded gray), as in ado-trastuzumab emtansine, or with a hindered disulfide-containing link (disulfide shaded gray) that is cleavable by reduction, as in mirvetuximab soravtansine (values for n and m are between 3 and 4 maytansinoids per antibody). The linker for mirvetuximab soravtansine also bears a hydrophilic charged sulfonate group.

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Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer by Kenneth J. Olivier Jr., Sara A. Hurvitz


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