Abstract
Cytotoxic fusion proteins for tumor therapy are composed of an antibody-based targeting moiety and an effector molecule. Effectors may possess enzymatic activity confering cytoxicity after internalization or be an antibody-targeted death-receptor ligand that induces apoptosis after interaction with a death receptor. In this review, we focus on cytotoxic fusion proteins which, in most cases, are composed of fully human targeting and effector moieties. Regarding the first category, as outlined above, we focus on fusion proteins based on ribonucleases, granzyme B, apoptosis-inducing factor and death-associated protein kinases. The second category of fusion proteins makes use of cell-death inducing ligands such as tumor-necrosis factor, tumor necrosis factor α-related, apoptosis-inducing ligand fas ligand and a tumor-targeting antibody moiety. For the latter category, prodrug-related concepts are also covered. The critical issues to be resolved for improved efficacy and safety are discussed.
- Cytotoxic enzyme effectors
- death receptors and corresponding ligands
- endosome escape
- immuno-RNAses
- granzymes
- apoptosis inducing factor
- cellular trafficking
- tumor targeting
- review
- Received December 16, 2012.
- Revision received March 6, 2012.
- Accepted March 7, 2012.
- Copyright© 2012 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved