Autoimmune and antitumor consequences of antibodies against antigens shared by normal and malignant tissues

There is now a considerable body of information documenting the autoimmune consequences of antibodies induced by growing malignancies, or by passively administered and actively induced antibodies, in cancer patients against antigens shared by normal and malignant tissues. This provides a rich source of information addressing the consequences of autoantibodies against a range of antigens. Antibodies against cell-surface or intracellular antigens in the central nervous system (CNS) or on epithelial surfaces of normal tissues do not generally result in autoimmunity, but the same types and titers of antibodies against cell surface antigens in the subepidermal skin, peripheral nerves, blood, or vascular sites such as the spleen and bone marrow readily induce autoimmunity. The blood brain barrier of the CNS and apical antigen expression and the basement membrane in epithelial tissues, may protect these sites from antibody induced damage. Cancer cells, however, are protected by neither unidirectional antigen expression nor basement membranes. Vaccine induced antibodies against a variety of cancer cell surface antigens have been associated with prevention of tumor recurrence in preclinical models and in vaccinated cancer patients, in the absence of demonstrable autoimmunity. This forms the basis for a series of ongoing Phase III trials with single or polyvalent antigen cancer vaccines designed for optimal antibody induction.