Antibody-cytotoxic agent conjugates for cancer therapy.
Antibody-based delivery of cytotoxic agents, including toxins, to tumours can dramatically reduce systemic toxicity and increase therapeutic efficacy. The advantage of a monoclonal antibody (mAb) is superior selectivity towards antigens expressed on the surface of cancer cells. Recent advances in biotechnology accelerated progress in the pharmaceutical applications of mAbs. A cytotoxic warhead is attached to a mAb in an immunoconjugate via a linker, which is stable in circulation but efficiently cleaved in the tumour tissue. The warhead, mAb and linker play important roles in the successful design of potent and efficient immunoconjugates. To date, one mAb-cytotoxic agent conjugate has been approved by the FDA and several other candidates are in various stages of clinical trials. This review describes the recent progress in the design and development of mAb-based immunoconjugates of cytotoxic agents, and summarises the criteria for the critical choices of a suitable mAb, linker and cytotoxic agent to design an efficacious immunoconjugate.
Chen
Jin
J
Institute of Chemical Biology & Drug Discovery, State University of New York, Stony Brook, 11794-3400, USA.
Jaracz
Stanislav
S
Zhao
Xianrui
X
Chen
Shuyi
S
Ojima
Iwao
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000922:Immunotoxins