Monoclonal antibody drug immunoconjugates for targeted treatment of cancer

Monoclonal antibodies (mAb) directed to tumor-associated antigens (TAA) or antigens differentially expressed on the tumor vasculature have been covalently linked to drugs that have different mechanisms of action and various levels of potency. The use of these mAb immunoconjugates to selectively deli...

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Bibliographic Details
Published inCancer Immunology, Immunotherapy Vol. 52; no. 5; pp. 328 - 337
Main Authors Trail, Pamela A, King, H Dalton, Dubowchik, Gene M
Format Journal Article
LanguageEnglish
Published Germany Springer Nature B.V 01.05.2003
Springer-Verlag
Subjects
Aminoglycosides
Anthracyclines - administration & dosage
Anti-Bacterial Agents - therapeutic use
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized
Antigens
Cancer therapies
Clinical Trials as Topic
Cytotoxicity
Drugs
FDA approval
Gemtuzumab
Humans
Immunotherapy
Immunotherapy - methods
Immunotoxins - therapeutic use
Monoclonal antibodies
Neoplasms - immunology
Neoplasms - therapy
Symposium in Writing
Toxicity
Tumors
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Summary:Monoclonal antibodies (mAb) directed to tumor-associated antigens (TAA) or antigens differentially expressed on the tumor vasculature have been covalently linked to drugs that have different mechanisms of action and various levels of potency. The use of these mAb immunoconjugates to selectively deliver drugs to tumors has the potential to both improve antitumor efficacy and reduce the systemic toxicity of therapy. Several immunoconjugates, particularly those that incorporate internalizing antibodies and tumor-selective linkers, have demonstrated impressive activity in preclinical models. Immunoconjugates that deliver doxorubicin, maytansine and calicheamicin are currently being evaluated in clinical trials. The feasibility of using immunoconjugates as cancer therapeutics has been clearly demonstrated. Gemtuzumab ozogamicin, a calicheamicin conjugate that targets CD33, has recently been approved by the Food and Drug Administration (FDA) for treatment of acute myelogenous leukemia (AML). This review concentrates on the properties of the tumor and the characteristics of the mAb, linker, and drugs that influence the efficacy, potency, and selectivity of immunconjugates selected for cancer treatment.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-002-0352-9