Allogeneic stem cell transplantation as immunotherapy for renal cell carcinoma: from immune enhancement to immune replacement.
The lack of efficacy of chemotherapeutics, radiotherapy, and cytokine-based immunotherapy has catalyzed the preliminary enthusiasm for nonmyeloablative stem cell transplants as a novel investigational tool for treating metastatic RCC. The observation that cytokine-refractory metastatic RCC may regress following allogeneic transplantation attests to the powerful nature of the graft-versus-tumor effect that results from this treatment modality. Pilot trials and recent in vitro data provide the first clear evidence that the graft-versus-tumor effect mounted against RCC can produce clinically meaningful regression of a metastatic solid tumor. Given this observation, the authors have begun to expand the investigational use of nonmyeloablative stem cell transplants to other treatment-refractory genitourinary tumors, including metastatic bladder and prostate cancer. It is hoped that future demonstrations of graft-versus-tumor effects in other solid malignancies will lay the groundwork for the development of tumor-targeted strategies that use allogeneic transplantation of donor lymphocytes as an immunotherapeutic platform. Further advances in systemic and selective immunosuppressive agents that limit acute GVHD hold the potential to decrease the toxicity associated with nonmyeloablative stem cell transplants and may ultimately broaden the clinical applicability of this approach.
Drachenberg
Darrel
D
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Childs
Richard W
RW
D002292:Carcinoma, Renal Cell / Q000628:therapy*; D020350:Graft vs Tumor Effect / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007680:Kidney Neoplasms / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D014184:Transplantation, Homologous