ABSTRACT
Burnet’s theory of immunosurveillance postulates that malignant transformation causes the expression of neoantigens. The theory states tumor specific antigens are recognized by the immune system, which then destroys the malignant cells.1 A role for the im mune system, especially T cells, in controlling cancer, is supported by the observation of a higher incidence of virus-associated cancer in immunocompromised patients compared to healthy individuals.2,3 Virally induced tumors only make up a minority (15%-20%) of all tumors.4'7 Although immunosurveillance is operational against virus-induced tumors this is still a matter of debate for non-virus induced tumors. However, for immunotherapy to have a wider application other targets besides viral targets need to be identified. Over the past decade new tumor antigens have been identified. Many of these new antigens are encoded by cellular genes representing unique tumor antigens, shared tumor-specific antigens and tissue specific differentiation antigens.8,9 The occurrence of natural T cell responses to these cellular antigens in cancer patients demonstrates the presence of a T cell repertoire which can react against tumor associated self antigens. Although promising targets for immunotherapy, these antigens are limited in their expression to certain types of tumors, particularly in the case of tissue specific differentiation antigens
Next to these antigens targets which are expressed in a wide variety of tumors are desir able. An additional property of choice would be direct involvement of target antigens in malig nant transformation, thereby reducing the possibility of immune escape. The tumor suppres sor protein p53 meets these requirements.
