Camel Single-Domain Antibodies as Modular Building Blocks to Make Bivalent Constructs for Use in Immunotherapy of Cancer

Abstract

Over the last years there has been a growing interest in the use of antibodies and antibody fragments as therapeutic entities to treat cancer. Identification of the smallest antibody fragment still capable of binding to antigen has progressed from full antibody molecules to Fab and recombinant single chain Fv fragments. A further reduction to single-domain binding proteins based upon immuno-globulin VH and VH-like domains is being pursued since they offer exciting prospects in the development of novel immunotherapeutics. Unfortunately, the poor solubility and reduced antigen affinity requires additional engineering. By serendipity, it was discovered that this engineering is already performed in nature. Part of the humoral immune response of camels and llamas is based largely on heavy-chain antibodies where the light chain is totally absent. These unique antibody isotypes interact with the antigen by virtue of only one single variable domain, referred to as VHH. Here we describe the properties of camel VHH that offer added value over conventional antibody fragments as treatment modality for tumour patients.