Monoclonal antibody therapeutics and apoptosis.
The potential for disease-specific targeting and low toxicity profiles have made monoclonal antibodies attractive therapeutic drug candidates. Antibody-mediated target cell killing is frequently associated with immune effector mechanisms such as antibody-directed cellular cytotoxicity, but they can also be induced by apoptotic processes. Antibody-directed mechanisms, including antigen crosslinking, activation of death receptors, and blockade of ligand-receptor growth or survival pathways, can elicit the induction of apoptosis in targeted cells. Depending on their mechanism of action, monoclonal antibodies can induce targeted cell-specific killing alone or can enhance target cell susceptibility to chemo- or radiotherapeutics by effecting the modulation of antiapoptotic pathways. This review will focus on the mechanisms by which antibodies are capable of eliciting programmed cell death either directly or indirectly within tumor cells.
Ludwig
Dale L
DL
ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. dale@imclone.com
Pereira
Daniel S
DS
Zhu
Zhenping
Z
Hicklin
Daniel J
DJ
Bohlen
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D008954:Models, Biological; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000922:Immunotoxins