Not all malignant cells progress to invasive
cancer, some may even regress, but the early detection of abnormal cells can be crucial for patient survival. Immune surveillance mechanisms are complex and provide continuous efforts for the removal of transformed cells. Naturally occurring
antibodies are frontier soldiers that act as the first line of defense in the battle against
cancer. During the process of
carcinogenesis naturally occurring antibody responses to
tumor antigens were found to be associated with improved survival and protection against the spread of
cancer. Using the human hybridoma technology, a series of
tumor-binding
antibodies can be isolated as they have several common features: they are germ-line coded
IgM antibodies, they bind to various
tumor-antigens, they induce apoptosis of malignant cells, and most importantly they detect not only malignant cells but also the precursor stages (i.e.,
autoantigens). Natural protective
autoantibodies against
tumor-antigens were isolated from patients and healthy donors reflecting the development of naturally occurring B-cell responses during the process of
cancer evolvement. They fulfill the definition of
autoantibodies since they are self-reactive and they also bind altered
self-antigens such as
tumor cells. In this regard various
autoantibodies such as anti-dsDNA and anti-Fas
autoantibodies were found to be significantly higher in patients with various
carcinomas, thus playing a role for their improved survival. Targeting T-regulatory cells, namely the expression of CTLA-4 was also found to improve survival in
cancer patients. Autoimmunity and
malignancy frequently coexist and they may share etiological and pathological mechanisms. Therefore, the efficacy of
intravenous immunoglobulins or CTLA-4 blockade was also employed as a treatment for prevention of
malignancy and
metastases spread.