Antibody-mediated receptor endocytosis: Harnessing the cellular machinery to combat cancer

Monoclonal antibodies targeting specific surface antigens of cancer cells are rapidly becoming the main stay drugs in specific diseases, such as lymphoma and breast cancer. Therapeutic antibodies almost invariably induce endocytosis of their antigens, and this attribute is already harnessed as a strategy to deliver cytotoxic payloads into cancer cells. The therapeutic potential, however, extends to direct antitumor activity of naked (unconjugated) antibodies, but the contribution of antibody-induced endocytosis to antitumor effects is variable and remains largely unclear. Interestingly, mixtures of monoclonal antibodies, each engaging a distinct epitope of the same antigen, synergistically induce receptor degradation and correspondingly collaborate in tumor inhibition. Here we describe several examples of therapeutic and experimental antibodies, with an emphasis on growth factor receptors and the possibility that future immunotherapy will employ specific antibody combinations, which robustly strip tumors of their most essential receptors.