Natural human immunoglobulins in cancer immunotherapy

The natural or innate immunity is the first-line defense against transformed cells. It guarantees the recognition and removal of malignant cells at an early stage and makes manifest cancers an exceptional event. Natural antibodies, which are predominantly IgM molecules, play a major role in these defense mechanisms and they have some typical features in common. They are coded by specific germline families and equipped mainly with lambda-chains, in contrast to the majority of circulating antibodies. The targets that are recognized by these antibodies are not newly synthesized proteins, but instead post-translationally modified carbohydrate structures on membrane-bound glycoproteins and glycolipids. Another typical feature of these natural IgM antibodies is their ability to induce apoptosis in vitro and in vivo in a death domain-independent manner. These results show that natural IgM antibodies represent a huge reservoir of therapeutic antibodies.