Human leukocyte differentiation antigens as therapeutic targets: the CD molecules and CD antibodies

The cell membrane presents an attractive target in a number of different disease situations. Most obviously, malignant cells may be killed by damaging their cell membranes. There are also more subtle, though effective, ways of rendering cells harmless by engaging proteins at the cell surface. The cells of the immune system may be targeted, for example to stop a damaging immune reaction, such as acute inflammation or rejection of a transplanted organ. If we are to make the best use of the opportunities to modulate disease by targeting the cell membrane, we need a detailed understanding of the many proteins, glycoproteins and glycolipids that are attached to or inserted in the cell membrane. The CD (cluster of differentiation) Workshops, more properly known as the HLDA (Human Leukocyte Differentiation Antigens) Workshops have, since 1982, focussed on the study of the membrane molecules of leukocytes, including the major cells of the immune system and malignant cells derived from them. The scope has extended to molecules on endothelium which are important in interaction with leukocytes. Many of the molecules characterised as leukocyte antigens are also expressed on other tissue. The approaches developed by the HLDA Workshops are useful in the study of the molecular composition and function of cells of other organ systems. Some of the antibodies produced in order to study the CD molecules have proved useful as therapeutic agents. This review describes the CD system, how it has developed and what it means and introduces the field of therapy based on antibodies against CD or similar molecules. The author is responsible for organising the next (8th) HLDA Workshop and invites readers to suggest ways in which the therapeutic relevance of the Workshop may be enhanced.