By Kenneth J. Olivier Jr., Sara A. Hurvitz
Providing sensible and confirmed strategies for antibody-drug conjugate (ADC) drug discovery good fortune in oncology, this booklet is helping readers enhance the drug safeguard and healing efficacy of ADCs to kill distinct 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 experiences of ADCs in oncology drug development
• Features contributions from highly-regarded specialists at the frontlines of ADC examine and development
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Additional resources for Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer
The use of these only moderately cytotoxic compounds as payloads for ADCs was at least one of the barriers to the successful execution of the ADC concept. The idea that conventional chemotherapeutic drugs were not potent enough to serve as payloads for ADCs has guided much of the subsequent research in the field [4–6]. 2 The Building Blocks of a Typical ADC All three parts of an ADC, the antibody, the cytotoxic payload, and the linker chemistry that joins them together, are important in designing an ideal ADC.
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.
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.