AUTOIMMUNITY AND CANCER - BENEFICIAL RELATIONSHIPS - A NEW CONCEPT FOR THE PRODUCTION OF HUMAN MONOCLONAL-ANTIBODIES (REVIEW)

Autoimmune diseases are the consequence of the immune system attack on the self. Autoimmunity, sometimes, is reflected through the productio n of autoantibodies to various self antigens leading to cellular malfu nction or destruction. In the current study we employ such autoantibod ies for the treatment of cancer originated from the respective normal cells. This concept is wide and entails many autoimmune disorders and diversity of malignant conditions. To illustrate the therapeutic and p ractical potential we depicted four examples: vitiligo and melanoma - vitiligo is considered dermatologic autoimmune disorder presented as d epigmented skin areas. The destruction of the pigmented cells (melanoc ytes) is mediated by autoantibodies. We have purified these anti-melan ocyte antibodies from patients with vitiligo and showed their cytotoxi c effect towards malignant melanoma cells in vitro and ill vivo; anti- phospholipid syndrome (APLS) and cancer-cancer cells differ from norma l cells by the expression of phosphatydilserine (PS) on their outer me mbrane surface. We have used such anti-PS autoantibodies, derived from patients with APLS, as effective treatment for melanoma in a murine s ystem; Autoimmune hemolytic anemia (AIHA) and hematological malignanci es - in patients with AIHA, the red blood cells (RBC) destruction is m ediated by binding of autoantibodies to RBC. We have shown the specifi c binding of these anti-RBC autoantibodies to RBC and to malignant cel ls of the erythroid lineage. Thus, these autoantibodies may have diagn ostic/therapeutic potential for conditions such as erythroleukemia and polycythemia vera; anti-lymphocyte antibodies and lymphoproliferative diseases - in SLE and other systemic autoimmune conditions autoantibo dies directed against lymphocytes can be found. These cytotoxic antibo dies can be targeted against lymphocytes of lymphoproliferative diseas es such as chronic lymphocytic leukemia, or lymphoma. The diversity of autoimmune diseases provides a great source for human preformed highl y specific autoantibodies which can be used as an effective immunother apy by themselves, for diagnostic purposes, as a cell specific carrier conjugated to other cytotoxic agents and in combined therapy in the c ombat against cancer.