Although data indicate that the immune system is of major importance for cancer control, malignant tumours continue to grow and the efficacy of immunotherapy is rather poor with an objective remission rate of 15-30%. There can be several reasons for this apparent paradox:                Tumours avoid the recognition by the immune system by not expressing tumour associated antigens properly        Tumour associated antigens (often self antigens), which are too weak to elicit an adequate immune response        Induction of tolerance        Cancer related immunosuppression, which prevents an adequate immune response        
These alternatives require completely different therapeutic strategies, either proper stimulation of the immune system or control of cancer related immunosuppressor mechanisms.
Immunosuppression in cancer is mainly characterized by: Reduced proliferative and cytotoxic capacity of lymphocytes, in particular tumour infiltrating lymphocytes, poor migration of inflammatory cells, reduced production and response to IL-2, difficulties to elicit an immune response by vaccination, also against other than tumour related antigens and pathological cytokine production. This dysregulation of the immune system results in poor immune mediated cancer control and a paraneoplastic syndrome (subfebrility, fatigue, anorexia, weight loss and deterioration of laboratory parameters).
Immunostimulatory therapeutic strategies using cytokines (e.g. interferons, interleukins) or vaccination, in order to enhance the immune mediated reactivity to the tumour, has been tried for several decades, but have so far had only very limited success. This indicates that immunostimulation in order to overcome a poor immune response in cancer patients might be suppressed by other so far unidentified mechanisms.
We have in two previous patent applications described two fundamental immunoregulatory mechanisms of relevance to all types of malignant tumours. In the first of these applications the importance of Fc-receptor modulation and ways to overcome this cancer related immunosuppression by modulating Fc-receptor cross-linking was demonstrated. In this patent application also proteolytic fragments of normally occurring proteins were demonstrated to induce pathological monokine production. In the second patent application some of these neo-structures were found to be integrin binding/blocking and their occurrence and immunoregulatory activity was further analysed by using monoclonal antibodies directed against albumin derived neo-structures. In the latter patent application also the occurrence and importance of auto-antibodies to these neo-structures is described.