Immunotherapy with antibodies: Tumor development, immune defense and therapeutic antibodies

Abstract

Tumor development is based on mutations of genes involved in cell growth (e.g. transcription factors, growth receptors or intracellular signal molecules) or in suppressor genes (e.g. p53). During tumor growth cell clones are selected, which contain driver genes, leading to uncontrolled growth of these cell clones. During all phases of tumor development (immunosurveillance, equilibrium phase, escape of the tumor from the immune system) the interaction between the immune system and the tumor cells and the development of a chronic inflammation in the tumor microenvironment play a crucial role. The aim of cancer immunotherapy is to activate the immune system. A promising immunotherapy is based on antibodies that activate immune cells, inhibit tumor growth or lead to destruction of tumor cells. Applied are recombinant IgG antibodies or genetically engineered antibody fragments against tumor-associated antigens (TAA’s). They are applied singularly or in combination with chemo- or radiotherapy. Promising are checkpoint antibodies, which abrogate blocking of cytotoxic CD8+ T cells and CD4+ T cells by tumor cells and/or dendritic cells. Other successfully applied antibodies are bispecific antibodies (recognize T‑cell and tumor cell), chimeric antigen receptors (CARs) for T cell therapy, immunocytokines (cytokines fused to antibodies) and immunotoxins (toxins fused to antibodies). In addition intracellular antibodies successfully tested in xenograft tumor mouse models have promising therapeutic potential.