Antibody-based therapeutics in oncology.
The recent clinical and commercial success of anticancer antibodies, such as rituximab (Rituxan) and trastuzumab (Herceptin) has created great interest in antibody-based therapeutics for hematopoietic malignancies and solid tumors. Given the likely lower toxicity for antibodies versus small molecules, the potential increase in 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, it is anticipated that current and future antibody therapeutics will find substantial roles alone and in combination therapy strategies for the treatment of patients with cancer. It is also likely that conjugation strategies will add new radiolabeled and toxin-linked products to the market to complement the recent approvals of ibritumomab tiuxetan (Zevalin) and gemtuzumab ozogamycin (Mylotarg). However, although there are a large number of agents in both early and later stages of clinical development, only a handful will make it through regulatory approval and become successful products. This review considers the structure of anticancer therapeutic antibodies, the techniques used to reduce their antigenicity, factors that influence efficacy and toxicity, conjugation with isotopes and toxins and antibody target validation.
Ross
Jeffreys
J
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA. rossj@mail.amc.edu
Gray
Karen
K
Schenkein
David
D
Greene
Barry
B
Gray
Gary S
GS
Shulok
Jeanine
J
Worland
Peter J
PJ
Celniker
Abbie
A
Rolfe
Mark
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins