Abstract | The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Antibody–drug conjugates are powerful new treatment options for lymphomas and solid tumours, and immunomodulatory antibodies have also recently achieved remarkable clinical success. The development of therapeutic antibodies requires a deep understanding of cancer serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system and cancer cells. This Review outlines the fundamental strategies that are required to develop antibody therapies for cancer patients through iterative approaches to target and antibody selection, extending from preclinical studies to human trials.
Monoclonal antibodies currently FDA approved in oncology and their mechanisms of action
| Naked antibodies: solid malignancies | |
| | |
| Trastuzumab (Herceptin) | Inhibition of ERBB2 signalling and antibody-dependent cellular cytotoxicity (ADCC) |
| Bevacizumab (Avastin) | Inhibition of VEGF signalling |
| Cetuximab (Erbitux) | Inhibition of EGFR signalling and ADCC |
| Panitumumab (Vectibix) | Inhibition of EGFR signalling |
| Ipilimumab (Yervoy) | Inhibition of CTLA4 signalling |
| | |
| Naked antibodies: haematological malignancies | |
| | |
| Rituximab (Mabthera) | ADCC, direct induction of apoptosis and complement-dependent cytotoxicity (CDC) |
| Alemtuzumab (Campath) | Direct induction of apoptosis and CDC |
| Ofatumumab (Arzerra) | ADCC and CDC |
| | |
| Conjugated antibodies: haematological malignancies | |
| | |
| Gemtuzumab ozogamicin (Mylotarg) | Delivery of toxic payload, calicheamicin toxin |
| Brentuximab vedotin (Adcetris) | Delivery of toxic payload, auristatin toxin |
| 90Y-labelled ibritumomab-tiuxetan (Zevalin) | Delivery of the radioisotope 90Y |
| 131I-labelled tositumomab (Bexxar) | Delivery of the radioisotope 131I, ADCC and direct induction of apoptosis |
| | |
Source: Antibody therapy of cancer. Andrew M. Scott (andrew.scott@ludwig.edu.au), Jedd D. Wolchok and Lloyd J. Old. Nature Reviews Cancer Volume 12 | Avril 2012 | 278-287.
Free paper available at :
Aucun commentaire:
Enregistrer un commentaire