ReviewManipulating T cell-mediated pathology: Targets and functions of monoclonal antibody immunotherapy

•There is a significant unmet need for Safe and specific T cell inactivating antibodies.•The TCR remains the most intriguing and efficacious target for inactivating T cells.•Depletion of T cells increases susceptibility to infection and malignancy.•Non-depletional highly specific T cells inactivation will be a primary future goal.

Monoclonal antibody (mAb) technology has revolutionized treatment options for T cell mediated diseases. However, a safe, clinically available anti-T cell antibody (ab) remains elusive. Experience with anti-T cell agents and their propensity for causing immune-mediated toxicities have hampered the development of anti-T cell mAb's. Furthermore, misunderstanding regarding mechanism(s) of action of particular antibodies can influence development and clinical prescription habits. For example, the anti-CD3 Ab OKT3 is consistently described as a depleting Ab even though original studies showed the mechanism to be non-lytic. Future anti-T cell mAbs are likely to be non-depletional and focused on the expansion of regulatory T cells. This review discusses how the properties of Abs can be exploited for manipulating pathological T cell responses in the clinic.