Role of immunotherapy in stem cell transplantation

Relapse of the underlying malignancy continues to be a major problem after both autologous and allogeneic stem cell transplantation. Over the years, it has been recognized that immune-mediated graft-versus-tumor effects are crucially involved in eliminating minimal disease and controlling its recurrence after stem cell transplantation. This recognition has led to a number of studies that have attempted to stimulate a cellular immune response in the recipient, especially after allogeneic transplantation. Immunotherapy after autologous transplantation has to take into consideration the fact that patients' immune cells frequently are compromised and tolerance to the host tumor may have developed. Hence, trials involving the administration of cytokines (such as with interleukin and interferon) have shown limited benefits. This situation is different for allogeneic transplantation for which the infusion of donor lymphocytes has shown disease regression, especially in patients with chronic leukemias. However, such treatment is effective only if the patient has limited disease, and severe graft-versus-host disease frequently has to be accepted as a complication. This fact has led investigators to pursue the generation of specific lymphocytes that can recognize tumor antigens but not necessarily induce graft-versus-host disease. Such studies are in the early stages, and although some promising results have been observed, it is unclear at this point if the antitumor effect can be separated sufficiently from the graft-versus-host disease mediated by allogeneic lymphocytes. More recently, it has been shown that natural killer (NK) cells can have an antitumor effect in myeloid malignancies, particularly if the cells are allogeneic and do not recognize self-HLA antigens. At this point, it appears that engineered T-lymphocytes and allogeneic NK cells may be useful in preventing or treating relapse after allogeneic transplantation. It remains to be seen if such novel cellular therapies can also be implemented after autologous transplantation via the use of engineered allogeneic immune cells.