Anticancer antibodies.
The recent clinical and commercial success of anticancer antibodies such as rituximab and trastuzumab has created great interest in antibody-based therapeutics for hematopoietic malignant neoplasms and solid tumors. Given the likelihood of lower toxic effects of antibodies that target tumor cells and have limited impact on nonmalignant bystander organs vs small molecules, the potential increased efficacy by conjugation to radioisotopes and other cellular toxins, and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, current and future antibody therapeutics are likely to find substantial roles alone and in combination therapeutic strategies for treating patients with cancer. It also is likely that conjugation strategies will add new radiolabeled and toxin-linked products to the market to complement the recent approvals of ibritumomab tiuxetan and gemtuzumab ozogamicin. This review considers the structure of anticancer therapeutic antibodies and the techniques used to reduce their antigenicity. Efficacy and toxic effects, conjugation with isotopes and toxins, and validation of the antibody targets also are discussed. Antibodies approved by the Food and Drug Administration are described in detail, as are antibodies in late and early stages of clinical development.
Ross
Jeffrey S
JS
Divisions of Molecular Medicine, Molecular Pathology, and Oncology Therapeutics, Millennium Pharmaceuticals, Cambridge, MA, USA.
Gray
Karen
K
Gray
Gary S
GS
Worland
Peter J
PJ
Rolfe
Mark
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D015202:Protein Engineering
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents