By Kenneth J. Olivier Jr., Sara A. Hurvitz
Providing sensible and confirmed strategies for antibody-drug conjugate (ADC) drug discovery luck in oncology, this ebook is helping readers increase the drug safeguard and healing efficacy of ADCs to kill detailed tumor cells.
• Discusses the fundamentals, drug supply ideas, 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 study and development
Read Online or Download Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer PDF
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Extra info for Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer
35 Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN‐35) in patients with 36 37 38 39 40 41 42 43 44 45 46 relapsed or refractory systemic anaplastic large‐cell lymphoma: results of a phase II study. Journal of Clinical Oncology 2012;30:2190–6. Foyil KV, Bartlett NL. Anti‐CD30 Antibodies for Hodgkin lymphoma. Current Hematologic Malignancy Reports 2010;5:140–7. Forero‐Torres A, Leonard JP, Younes A, et al. A Phase II study of SGN‐30 (anti‐CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma.
However, such modalities have proven only partially effective at the maximum achievable doses, limited by the severe side effects of the cytotoxic agents used. Attaching cytotoxic effector molecules to an antibody to form an antibody–drug conjugate (ADC) provides a mechanism for the selective delivery of the cytotoxic payload to cancer cells via the specific binding of the antibody moiety to cancer-selective cell surface molecules. 1). Furthermore, conjugation of a small molecular weight cytotoxic agent to a large hydrophilic antibody protein is expected to restrict penetration of the cytotoxic compound across cellular membranes of antigen-negative normal cells, providing an additional mechanism by which the therapeutic index of the small molecule cytotoxin is widened, beyond that of targeted delivery.
Recently, however, the World Health Organization decided to alter criteria for providing generic names to antibodies, resulting in the confusing situation of many humanized antibodies being given names bearing the suffix of a chimeric antibody (“-ximab”), for example, the anti-CD19 antibody, coltuximab [15, 21], and the antifolate receptor alpha (anti-FRα) antibody, mirvetuximab , both of which were humanized by the resurfacing method [15, 23]. 1 Antibody Isotype in ADCs Most of the antibodies utilized in ADCs evaluated in clinical trials to date, including those (about 20) now discontinued, have been of the human IgG1 isotype (60 of 67 ADCs, with an additional four not disclosed, upon this author’s 7 8 Antibody-Drug Conjugates review of source information).
Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer by Kenneth J. Olivier Jr., Sara A. Hurvitz