Additional therapeutic applications of monoclonal antibodies

Thus far, Lhe discussion relaling to the medical uses of monoclonals has focused exclusively upon cancer. Monoclonal antibodies (and their derivatives), however, have a far broader potential therapeutic application. Actual/potential additional uses include detection and treatment of cardiovascular disease, infectious agents, and various additional medical conditions (Table 13.2). 

Various antibody preparations have been developed that facilitate imaging of vascular-related conditions, including myocardial infarction, deep vein thrombosis and atherosclerosis. Anti-myosin monoclonal antibody fragments (Fab) labelled with mIn, for example, have been used for imaging purposes in conjunction with a planar gamma camera. The antibody displays specificity for intracellular cardiac myosin, which is exposed only upon death of heart muscle tissue induced by a myocardial infarction (heart attack). 

It has been estimated that 1-2 per cent of the US population suffer from autoimmune conditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an autoimmune response results from the inappropriate activation of a specific subset of B- and/or T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases is to induce depletion of the individual s T- and B-cell populations. This could be achieved by administration of an antibody raised against a surface antigen present on such cells. Initial trials, for example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glycoprotein present on many T-lymphocytes) over 7 days significantly reduced the clinical symptoms of rheumatoid arthritis for several months. 

Antibodies have and likely will find additional use in transplantation-related medicine. In general, cell-mediated immunological mechanisms are responsible for mediating rejection of transplanted organs. In many instances, transplant patients must be maintained on immunosuppressive drugs (e.g. some steroids and, often, the fungal metabolite cyclosporine). However, complications may arise if a rejection episode is encountered that proves unresponsive to standard immunosuppressive therapy. Orthoclone OKT-3 was the first monoclonal antibody-based product to find application in this regard. 

This antibody is raised against the protein-based CD3 antigen, present on the cell surface of most T-lymphocytes. I.v. administration of (unconjugated) antibody appears to block normal functioning of such T-cells and promote their clearance from the blood. However, upon cessation of antibody administration, CD3 positive cell numbers rapidly revert to normal values. Therefore, maintenance immunosuppressives (e.g. with cyclosporine) must subsequently be restored. 

Deep vein thrombosis refers to clot formation within the vascular system, usually in the lower extremities. It requires prompt medical attention, as it not only disrupts blood flow in the affected area but can also lead to the formation of emboli, with serious, often fatal, medical consequences (Chapter 9). Such thrombi may be pinpointed by immunoscintigraphy, utilizing a radio-labelled antibody directed against platelets or, more often, flbrin. 

Atherosclerotic plaque also forms a target for imaging monoclonals. Most often, the antibodies employed display specificity for activated platelets, usually found in association with ruptured plaque. 

Various monoclonal preparations are also being assessed with regard to their ability to inhibit progression of various viral diseases. In most instances, the antibodies are capable of selectively 

---