Allogeneic Hematopoietic Blood-Cell Transplantation As Immunotherapy for Metastatic Renal Cell Carcinoma

Abstract

Once metastatic, the prognosis of patients with metastatic renal cell carcinoma (RCC) is extremely poor. Chemotherapy is usually ineffective, and radiotherapy is typically reserved for palliative purposes. Although most would consider RCC to be an “immunoresponsive” solid tumor, the vast majority of patients treated with systemic immunomodulators fail to manifest a disease response. Nevertheless, kidney cancer remains one of the few solid tumors to manifest evidence of intrinsic vulnerability to immune attack. As a result, considerable efforts have been made to develop methods to direct the immune system against RCC, including treatment with cytokines (e.g., interleukin [IL]-2, IL-12, interferons), the adoptive infusion tumor-infiltrating lymphocytes (TIL) or lymphocytes activated by cytokines (lymphokine-activated killer cells [LAK]) and tumor vaccine-based approaches. More recently, investigators have begun to pursue an alternative immune-based strategy in patients who fail to respond to conventional cytokines—namely, immune enhancement via total immune replacement following “low-intensity” nonmyeloablative allogeneic stem-cell transplantation (NST). NST has recently been shown to produce potent immune-mediated antitumor responses against a variety of chemotherapy-refractory hematologic malignancies, and has been associated with lower morbidity and mortality rates than conventional “mega-dose” myeloablative regimens.