Immunity and gene therapy: Benefits and risks

Congenital immunodeficiencies (ID) are unfortunate experiments of Nature that impair immunity. It is only fair that, by fortunate experiments of man, they may be cured. This was first true by 1968, when an X-linked ID became the first human disease successfully cured by bone marrow transplantation, now a standard therapeutic procedure for many other disorders including cancer. Of course, serious adverse events were reported, such as graft versus host disease. More than 30 years later, the same ID has become the first to be cured by gene therapy. Hurdles lie ahead, as the development of T cell leukaemia by insertional oncogenesis in two patients has painfully demonstrated. Immunity itself may become a hurdle for gene therapy when directed against the vector or even the therapeutic protein. But gene therapy is here to stay. Cancer, infectious diseases including Acquired Immunodeficiency Syndrome (AIDS), and other congenital disorders are next down the pipeline. As already shown for transplantation, the overall benefits may well be worth the risks.