Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 16, Issue 7, Pages 1037-1058Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.16.7.1037
Keywords
antibodies; anticancer prodrugs; cancer chemotherapy; drug targeting; polymer therapeutics
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Coupling of low molecular weight anticancer drugs to antibodies, serum proteins or polymers through a cleavable linker has been an effective method for improving the therapeutic index of cytotoxic established agents. Modern drug-antibody conjugates that have recently entered clinical trials have primarily used highly potent drugs such as calicheamicin or maytansins. Gemtuzumab ozogamicin, a conjugate of calicheamicin and an anti-CD33 humanized antibody, is the first drug-antibody conjugate to receive market approval. Drug conjugates that have undergone clinical assessment include N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates with doxorubicin, camptothecin, paclitaxel and Pt(II) complexes, poly(ethylene glycol) conjugates with camptothecin and paclitaxel, polyglutamate conjugates with paclitaxel and camptothecin, a methotrexate-albumin conjugate and an albumin-binding doxorubicin prodrug. This review summarizes the Phase I - III studies that have been performed with these macromolecular prodrugs.
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