Get 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 suggestions for antibody-drug conjugate (ADC) drug discovery luck in oncology, this ebook is helping readers enhance the drug protection and healing efficacy of ADCs to kill distinctive 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 examine and development

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

Example text

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].

Gemtuzumab ozogamicin and inotuzumab ozogamicin are conjugates of a calicheamicin payload where the linker includes an acid-labile hydrazone moiety (shaded gray), and also contains a hindered disulfide bond cleavable by reduction (average DAR of these ADCs are in the range of 2 to 4 – only one linker-payload structure drawn for simplicity). 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).

New York: Humana Press; 2013. Petersdorf SH, Kopecky KJ, Slovak M, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 2013;121:4854–60. Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta‐analysis of individual patient data from randomised controlled trials. Lancet Oncology 2014;15:986–96. O’Hear C, Rubnitz JE.

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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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