Human CD Antigens

CD antigens nomenclature

There are molecules with descriptive names which achieved widespread use before the availability of mAbs but where the descriptive name turned out to be misleading. The CD name is no more difficult to remember than a three-letter gene name. Therefore, it is likely that the CD-numbered molecules will continue to grow in number, that the names will be used more for some molecules and less for others, which have good alternative names and that antibodies which have been through the CD Workshops will continue to be used in preference to antibodies that have not. The activity of an antibody preparation and particularly its non-specific reactivity, will depend on the detailed history of that particular preparation. Different antibodies against the same CD molecule may behave quite differently because of differences in target epitope or affinity. The fact that an antibody has a CD number does not guarantee predictable behavior but it is far preferable to using an antibody without a CD classification.

CD molecules as targets for therapy

The cell membrane is the obvious place to attack a cell if you want to kill it, and antibodies, under the right conditions, provide the right ligands. The binding of ligands to cell surface molecules can have more subtle but equally useful effects - cells may be activated, induced to differentiate, or inhibited from responding to activation-inducing signals or differentiation inducing signals. Under the right conditions, antibodies can take the place of the natural ligands in these processes.

Table 1. CD molecules targeted in therapeutic applications.
(Expert Opinion on Biological Therapy, 2001)

CD antigens as drug target

Immunosuppression. OKT3, which is an antibody against CD3, a component of the T-cell receptor, is used to reverse T-cell-mediated rejection of organ transplants. It does this principally without killing the target T-cells; the T-cells continue to circulate but have downregulated their CD3 and are therefore ineffective in attacking the transplanted tissue. OKT3 also activates T-cells, in the sense that it stimulates them to release cytokines. This cytokine release response is an unwanted side effect in the context of transplantation, although it might be a desirable response in other situations. OKT3, as a foreign protein, is immunogenic in humans. The immune response to OKT3 is probably muted because the patients are immunosuppressed, but nevertheless limits treatment. OKT3 thus illustrates some of the effects that can be achieved in vivo with antibody against cell-surface determinants and also illustrates some of the constraining factors. Antibodies against other lymphocyte surface molecules have been used to dampen down the immune response in transplantation and in auto-immune disease. Several of these specificities illustrate different aspects of the multiple opportunities offered by antibodies against surface antigens. Bone marrow transplantation represents a special case, where the major problem is usually not rejection of the transplant but rather an immunological attack by the transplanted immune cells on the tissues of the recipient (the graft versus host reaction).

Cancer therapy. The control and eradication of tumors by antibodies has a history much longer than that of mAbs and the CD system. The principles are straightforward and there is a body of literature demonstrating success in animal models but clinical success has been slow in coming and sporadic.