Cancer therapeutic antibodies come of age: targeting minimal residual disease

Abstract

Ten years after the first clinical application of Rituximab, an anti-CD20 recombinant monoclonal antibody, immunotherapy has become common practice in oncology wards. Thanks to the great diversity of the immune system and the powerful methodology of genetic engineering, the pharmacologic potential of antibody-based therapy is far from exhaustion. The recent application of Trastuzumab, an antibody to a receptor tyrosine kinase, in adjuvant breast cancer therapy marks the beginning of a new phase in cancer treatment. Here we discuss molecular mechanisms of antibody-based therapy, the emerging ability to target minimal disease and the therapeutic potential of combining antibodies with other modalities.

Figure 1

Mechanisms of action of therapeutic antibodies. Binding of mAbs (orange) to antigens (green) on target cells can induce complement binding (via the C1 component) and activate ADCC, which requires interaction between the Fc portion of the antibody and FcγR molecules on effector cells, such as natural killer (NK) lymphocytes. Angiogenesis and cell growth are inhibited through downregulation of the vascular endothelial growth factor (VEGF) and mAbs interfering with growth factor (GF) binding, respectively. Intracellular degradation of surface antigens is preceded by endocytosis (internalization) of antigen‐bound mAbs (e.g., Trastuzumab). In the case of Rituximab, apoptosis occurs upon tyrosine kinase signaling and mobilization of intracellular calcium.