By Kenneth J. Olivier Jr., Sara A. Hurvitz
Providing functional and confirmed strategies for antibody-drug conjugate (ADC) drug discovery good fortune in oncology, this ebook is helping readers enhance the drug defense and healing efficacy of ADCs to kill detailed tumor cells.
• Discusses the fundamentals, drug supply techniques, pharmacology and toxicology, and regulatory approval strategies
• Covers the behavior and layout of oncology scientific trials and using ADCs for tumor imaging
• Includes case reviews of ADCs in oncology drug development
• Features contributions from highly-regarded specialists at the frontlines of ADC learn and development
Read Online or Download Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer PDF
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Additional info for Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer
Bonds between the linker and the side-chain amino group of the lysine. 7), and in the other maytansinoid ADCs in clinical development, as well as in calicheamicin-containing ADCs, such as gemtuzumab ozogamicin and inotuzumab ozogamicin [35, 39, 40]. 7, include ADCs with an acid-labile hydrazine linker (the calicheamicin conjugates), an uncleavable linker (ado-trastuzumab emtansine), and a hindered disulfide linker cleavable by the reduction of the disulfide bond (mirvetuximab soravtansine). 7 Examples of typical ADCs conjugated at lysine residues.
Such peptide mapping techniques provide a fingerprint that can be used to compare different lots of an ADC to ensure process consistency and robustness during scale-up to commercial manufacturing. 2 Conjugation of Payloads to Antibodies at Cysteine Residues Linker–payload constructs designed for attachment to sulfhydryl groups of cysteine residues of the antibody have made use of the rapid reaction between maleimido groups and sulfhydryl groups to form thioether bonds [31, 42, 51]. The auristatin (MMAE) used as the payload of the approved ADC, brentuximab vedotin, and the auristatins used in the other ADCs in current clinical development, which use this payload class (MMAE and MMAF), are synthesized as maleimide-bearing linker–payload compounds for reaction with protein sulfhydryl groups.
Oncologist 2007;12:577–83. 23 US Food and Drug Administration FDA Approves New Treatment for Chronic Lymphocytic Leukemia. FDA; 2009. 24 Fong L, Small EJ. Anti‐cytotoxic T‐lymphocyte antigen‐4 antibody: the first in 25 26 27 28 29 30 31 32 33 an emerging class of immunomodulatory antibodies for cancer treatment. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 2008;26:5275–83. Ascierto PA, Kalos M, Schaer DA, Callahan MK, Wolchok JD. Biomarkers for immunostimulatory monoclonal antibodies in combination strategies for melanoma and other tumor types.