Clinical development of a new class of oncology drugs

Immunotherapy has recently emerged as an effective treatment of cancer. While immune cells are often present in tumors, they are insufficiently activated to orchestrate an immune attack and may even be programmed to assist tumor development. Research in pre-clinical mouse tumor models has resulted in the development of several concepts that allow re-programming of these immune cells, resulting in immune-mediated attack of the tumor and tumor regression. Recently, one of these concepts has been successfully translated into immunotherapeutic drugs approved for patient treatment. These drugs are antibodies directed against inhibitory receptors (CTLA-4, PD-1) expressed at the surface of T-lymphocytes. By blocking negative signals, these ‘checkpoint inhibitors’ can unleash anti-tumor immunity that results in significant clinical benefit in certain groups of cancer patients.

An alternative approach towards immune cell activation involves the delivery of signals to activatory receptors on immune cells through antibodies, thereby supplementing stimulatory signals that are lacking in the tumor microenvironment. Experiments in mouse models have shown that these agonist immunostimulatory antibodies (IS-Abs) are at least as potent as the checkpoint inhibitors in activating therapeutic anti-tumor immunity. The mission of the IACT consortium is to translate the concept of agonist IS-Abs to clinically approved drugs and treatments.