Traitement par lymphothérapie adoptive des infections virales chez les patients transplantés : de réelles raisons d'espérer

The immunosuppressive drugs used to prevent graft rejection in transplant patients create a favorable environment for viral infections. These frequent and diverse infections can have deleterious effects on graft survival and can complicate medical follow-up of graft recipients. Several antiviral drugs, in particular those that target herpes viruses such as CMV, are available for treatment of viral infections frequently encountered by transplant patients. However, for many viral infections no effective drugs are available, and the usage of current drugs is limited by their lack of specificity and toxic side effects. Moreover, the current practice is to lengthen the duration of antiviral treatment, which may favor the selection of resistant viruses and worsen toxic drug effects. The immunosuppression induced in transplant patients to prevent graft rejection severely restricts the crucial antiviral activity normally assured by T lymphocytes. One therapeutic strategy to compensate for this deficit is to inject T lymphocytes selected and characterized ex vivo for their antiviral activity. Since the beginning of the 1990s, various approaches for adoptive antiviral lymphotherapy have been in active development in renowned cell therapy centers. Hundreds of patients have been included in phase I or II clinical trials, and the first phase III trials are underway. Although the strategies for the production of such lymphocytes vary (amplification in culture or direct selection of antiviral lymphocytes from peripheral blood), all studies so far demonstrate not only the feasibility and antiviral efficacy of such treatments but also a very favorable patient tolerance. In the context of antiviral lymphocyte treatment for patients under immunosuppression, we illustrate here in examples of the favorable results obtained following treatment of CMV, EBV, or adenovirus infections in transplant patients.