[Therapeutic monoclonal antibodies in oncology]

Abstract

Advances in bioengineering have lead to the possibility to conduct large scale production of monoclonal antibodies (MoAB) and to reduce progressively the murine component from 30% (chimeric MoAB) to 5% (humanized MoAB) to 0% (human MoAB). Three types of extracellular components are targeted in solid tumours: (1) Growth factors with transmembrane tyrosine kinase receptors either of tumour cells (IGF1) or endothelial cells (Bevacizumab). Bevacizumab has activity additive to that of chemotherapy in advanced colorectal, non squamous lung, ovarian, metastatic breast cancers and glioblastomas; (2) Extracellular domain of those transmembrane receptors: EGFR in colorectal cancer if no activating of KRAS with cetuximab and panitumumab, head and neck carcinomas with radiotherapy, and probably squamous lung cancers. Anti-ERBB2 MoAb are now a constitutive part of therapy of ERBB2 positive breast cancers at any stage; (3) Differentiation cluster regulating relationship ot tumour and stromal cells and in particular immunologic effectors. This is the case of anti-CTLA4 MoAB ipilimumab which activates and amplifies immunological cytotoxic response against melanoma with improved survival. These activities are achieved to the expense of class, target related toxicity conditioned by expression of the target on normal cells and or mechanism of action (immunological toxicity with ipilimumab). Of note a synergistic or additive activity with valid treatment regimens of targeted cancers and now targeted small molecules.