Abstract：
:Paclitaxel (Taxol) is a chemotherapeutic agent that prevents disassembly of microtubular polymers, causing a growth arrest in the G2-M phase of the cell cycle and leading to apoptotic death. Paclitaxel has remarkable efficacy against fast-growing tumors but possesses major drawbacks, such as poor solubility and lack of tumor selectivity. Conversely, monoclonal antibodies usually have low therapeutic efficacy but are highly soluble and selectively target tumor markers overexpressed in cancer cells. Therefore, to improve the therapeutic index of taxanes as chemotherapeutics, the high toxicity of paclitaxel was combined with the high selectivity and solubility of monoclonal antibodies as targeting agents. We report the chemical coupling and characterization of paclitaxel-antibody conjugates for treatment of neuroectoderm-derived tumors. Paclitaxel-antibody conjugates afforded selective toxicity toward cells expressing the target marker and were more cytotoxic in vitro than equimolar concentrations of free paclitaxel or free paclitaxel plus free antibody. In an in vivo model of xenografted tumors, systemic administration of paclitaxel-antibody conjugates prevented tumor growth and prolonged survival of mice better than free drugs. In addition, paclitaxel-antibody conjugates were highly soluble in water and stable at -20 degrees C for at least 3 months. These studies may lead to an increase or an improvement of the armamentarium and selectivity of cytotoxic agents.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Guillemard V,Saragovi HUsubject
Has Abstractpub_date
2001-01-15 00:00:00pages
694-9issue
2eissn
0008-5472issn
1538-7445journal_volume
61pub_type
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