Therapeutic monoclonal antibodies

Abstract

Monoclonal antibodies have been used extensively over the last few years in clinical trials of rheumatoid arthritis (RA). Not only are they potential therapeutic agents, but they are also useful probes into the immunopathogenesis of RA. Anti-tumour necrosis factor alpha (TNF alpha) monoclonal antibodies have been shown to be clinically efficacious. Although they produced rapid disease amelioration, the duration of clinical improvement was limited to 4-6 weeks. Re-treatments were again effective but long-term studies are required to assess their therapeutic role in RA. So far, the therapeutic effects of lymphocyte-depleting antibodies have been disappointing. From the data, it is clear that synovial lymphocytes are more difficult to eliminate than peripheral blood lymphocytes and it is likely that in order to delete all synovial lymphocytes, high doses of depleting antibodies will be required which could lead to severe immunosuppression. Hence, lymphocyte depletion may not be a feasible therapeutic strategy. However, there are a number of clinical trials currently underway attempting to inhibit CD4 lymphocyte function by non-depleting antibodies. In animal models of RA, such antibodies have been shown to induce long-term disease remission. Another possibility is to combine several monoclonal antibodies in order to induce disease remission in RA. This strategy has been used in murine collagen-induced arthritis in which a combination of anti-CD4 and anti-TNF alpha monoclonal antibodies was shown to be synergistic.