Programmed Death-1: Therapeutic Success after More than 100 Years of Cancer Immunotherapy

摘要

More than 120 years ago William Coley first tested the concept of manipulating the immune system to fight cancer by using bacterial products to treat patients with solid tumors. Low reproducibility and efficacy and serious side effects led to a low acceptance in the clinic. At the beginning of the 20th century Paul Ehrlich, the father of modern immunology, introduced the concept of the use of antibodies to target diseases, nowadays often referred to as the "Magic Bullet". He proposed that the immune system might control cancer. The introduction of the hybridoma technology for the production of monoclonal antibodies by Cesar Milstein and Georges J. F. Kohler in 1975 has led to the clinical introduction of multiple antibodies to fight cancer. Truly immune-stimulating approaches included the landmark trials of interferon-a and later high doses of interleukin-2 (IL-2) as well as so-called lymphokine-activated killer cells in patients with multiple tumor types.