Developing T-cell therapies for cancer in an academic setting

The development of targeted drug therapies for cancer has been a long-term ambition of clinicians and researchers alike. While most effort has been expended on identifying small molecule therapeutics, the immune system can be manipulated to provide biological components that will be the most targeted of all. Exploitation of the humoral immune system by manufacture of monoclonal antibodies has already been proven highly effective for treatment of many tumors.¹ The successful manipulation of the cellular component of the immune response, however, has been somewhat slower. In part, this is because of the complexity of developing and manufacturing the cellular components, and in part also, because our understanding of cellular physiology and function has been less extensive and detailed. Immunotherapies based on dendritic cells appear promising and adoptive therapy with T lymphocytes is also finally gaining traction. The use of T cells in cancer has a number of potential advantages: They have high targeting specificity They are capable of recognizing internal antigens if these are processed and presented on the tumor cell surface They have a good biodistribution and are able to actively traffic through multiple tissue planes They kill their target cells through a wide range of effector mechanisms so that resistance to all of these in a single cancer cell is unlikely They are self-amplifying - so that a small number of cells administered initially has the potential to expand to numbers sufficient to eradicate even bulky tumors