Antibody-targeted drugs for the therapy of cancer.
The advent of monoclonal antibodies has revitalised the concept of magic bullets and various agents (eg. drugs, toxins and isotopes) have been conjugated to monoclonal antibodies for selective delivery to tumours. Preclinical studies in mouse tumour models have been impressive and have lead to several clinical trials. These phase I trials have been less impressive. However, keeping in mind the aim of Phase I trials, the safety of using these conjugates in humans have been established. Several, major problems still remain to be overcome before these agents may be useful for the treatment of cancer. These problems stem from the nature of tumour vasculature, cytotoxic activity of the moiety linked to antibody and the targeted tumour antigen expressed on the cell surface. This review will deal with these various aspects described above and possible approaches to overcome these obstacles with a definite bias towards drug-monoclonal antibody conjugates. However, these concepts are equally applicable for improved targeting of other agents.
Pietersz
G A
GA
Austin Research Institute, Austin Hospital, Heidelberg Vic, Australia.
Krauer
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000235:genetics / Q000378:metabolism; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018796:Immunoconjugates