Antibody-targeted chemotherapy with immunoconjugates of calicheamicin.
Targeted delivery of cytotoxic agents to tumours is believed to improve both their anti-tumour efficacy and their safety. Antibodies specific for tumour-associated antigens have been used to deliver cytotoxic agents to tumour cells. Calicheamicin is a potent cytotoxic agent that causes double-strand DNA breaks, resulting in cell death. When conjugated to monoclonal antibodies specific for tumour-associated antigens, calicheamicin exerts strong antigen-specific anti-tumour effects against human tumour xenografts in preclinical models. Antibody-targeted chemotherapy with immunoconjugates of calicheamicin, exemplified by gemtuzumab ozogamicin (Mylotarg), is a clinically validated therapeutic strategy for the treatment of human cancer.
Damle
Nitin K
NK
Oncology Discovery Research, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. damlen@wyeth.com
Frost
Philip
P
D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules; D002986:Clinical Trials as Topic; D053281:Enediynes; D000079982:Gemtuzumab; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000080045:Inotuzumab Ozogamicin; D037102:Lectins / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D051918:Sialic Acid Binding Ig-like Lectin 2
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D053281:Enediynes; D018796:Immunoconjugates; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; C055955:calicheamicin gamma(1)I; D000079982:Gemtuzumab; D000080045:Inotuzumab Ozogamicin