Immune-gene therapy for renal cancer: chimeric receptor-mediated lysis of tumor cells

The immune system serves as a protective system against infectious agents such as bacteria, viruses and parasites. Foreign molecules (antigens) can be recognized by the immune system and induce an immune response resulting in destruction and elimination of the pathogens. In addition to infectious agents, also tumor cells can distingnish themselves from normal cells either by quantitative and/or qualitative different expression of genetic information. This idea forms the basis of cancer immunotherapy, which aims at the elimination of tumor cells using the patient's natural immune system. The concept of tumor-specific immune reactivity goes back to the postulation of immunesurveillance as formulated by Ehrlich in 1909 and adapted by Burnet in 1970. They proposed that the immune system might be capable of eliminating tumor cells in the same way that protects us from foreign agents, i.e. immunosurveillance. Although there might be immunesurveillance, this mechanism is not dominant, as tumor cells may escape the immune system resulting in uncontrolled cell proliferation and tumor formation. Therefore, effective anticancer immunotherapy should be directed at the manipulation and enhancement of the immune capacity to fight cancer cells. This can be accomplished either in an active way, by activating and amplifying the destructive potential of the individual's endogenous immune cells able to recognize and destroy the tumor, or in a passive way by providing ex vivo activated immune cells with anti-tumor capacity to a tumor-bearing individual.