Allogeneic hematopoetic stem cell transplantation for cytokine refractory renal cell carcinoma.

Abstract

The treatment options for patients who develop metastatic renal cell carcinoma (RCC) are few. Conventional chemotherapeutics and radiotherapy rarely result in clinically beneficial responses. Fortunately, the past two decades has seen the development of promising immunotherapeutic approaches to treat metastatic RCC including the use of cytokines such as interleukin-2 and interferon-a, the adoptive infusion of lymphokine activated killer cells and tumor-infiltrating lymphocytes (TIL), and recently the development of dendritic cell based vaccination strategies. The promising results from these studies have forged the path for ongoing immunologically-based investigational approaches. Reduced intensity or nonmyeloablative allogeneic stem cell transplantation (NST) has recently been shown to produce potent immune-mediated anti-tumor responses in a variety of chemotherapy refractory hematologic malignancies while being associated with less morbidity and mortality compared to conventional “high dose” myeloablative regimens. Knowledge of RCC’s proclivity to be regulated by the immune system recently led investigators to test this type of transplant strategy in this malignancy. Pilot trials were based on the hypothesis that graft versus tumor (GVT) effects, analogous to the graft-vs-leukemia (GVL) effect seen in hematological malignancies, might be generated against an immuno-sensitive solid tumor following the transplantation of allogeneic donor T lymphocytes. The recent observation of regression of metastatic RCC following NST has confirmed the susceptibility of RCC to a GVT effect. Disease responses have been seen in patients who have failed traditional cytokine regimens and have occasionally included complete responses. Here we review the development and outcome of pilot immunotherapy trials based on the use of an allogeneic immune system.