Fully human targeted cytotoxic fusion proteins: new anticancer agents on the horizon
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...
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Published in | Cancer genomics & proteomics Vol. 9; no. 3; pp. 119 - 133 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Greece
01.05.2012
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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. |
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AbstractList | 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 alpha -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 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. |
Author | Weidle, Ulrich H Georges, Guy Brinkmann, Ulrich |
Author_xml | – sequence: 1 givenname: Ulrich H surname: Weidle fullname: Weidle, Ulrich H email: ulrich.weidle@roche.com organization: Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, Im Nonnenwald 2, D-82377 Penberg, Germany. ulrich.weidle@roche.com – sequence: 2 givenname: Guy surname: Georges fullname: Georges, Guy – sequence: 3 givenname: Ulrich surname: Brinkmann fullname: Brinkmann, Ulrich |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22593247$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Animals Antibodies - chemistry Antibodies - immunology Antineoplastic Agents - chemistry Antineoplastic Agents - immunology Antineoplastic Agents - pharmacology Drug Delivery Systems Genetic Engineering Humans Immunotoxins - chemistry Immunotoxins - immunology Immunotoxins - pharmacology Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - pharmacology |
Title | Fully human targeted cytotoxic fusion proteins: new anticancer agents on the horizon |
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