mardi 27 mars 2012

Focus: Antibody therapy of cancer

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)

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 (, Jedd D. Wolchok and Lloyd J. Old. Nature Reviews Cancer Volume 12 | Avril 2012 | 278-287.
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