Monoclonal antibodies that recognize activated human lymphocytes - Experimental and clinical studies
Friend PJ., Tighe H., Waldmann H., Lim S., Collier St. DJ., Campbell D., Thiru S., Calne R.
The objective of this study was to evaluate, in an experimental model, three monoclonal antibodies that recognize antigens whose expression on the surface of human T lymphocytes is either specific to activation or greatly increased on activation and to proceed to clinical studies if an antibody were shown to have significant immunosuppressive properties. The experimental study demonstrated substantial immunosuppressive properties of Campath-6 and YTH 655 as shown by a doubling of the survival times of renal allografts between strongly mismatched baboons. Campath-2 was not shown to have any immunosuppressive effect; there are various possible explanations for this including rapid modulation or failure to direct baboon effector mechanisms. Campath-6 and YTH 655 are effective only by blocking functional molecules rahter than by cell deletion. The clinical pilot study of Campath-6, being both small and uncontrolled, does not provide unequivocal evidence of any beneficial effect of Campath-6. However, this group of patients was unusually free of early acute cellular rejection, and no patients was seen to have any ill effects or reactions after treatment (as was also the case in baboons). On this basis, we have proceeded to design a randomized, controlled trial of Campath-6 used prohylactically after liver transplantation; this is currently in progress.