%0 Journal Article
%T Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma
%A Clara E. J£¿kel
%A Stefan Hauser
%A Sebastian Rogenhofer
%A Stefan C. M¨¹ller
%A P. Brossart
%A Ingo G. H. Schmidt-Wolf
%J Journal of Immunology Research
%D 2012
%R 10.1155/2012/473245
%X Metastatic renal cell carcinoma (RCC) seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK) cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells. 1. Biology of Renal Cell Carcinoma and Current Treatment Options Renal cell carcinoma (RCC) accounts for nearly 3% of all adult malignancies. Metastatic RCC has a particularly poor prognosis with an overall survival of 12 months and a 5-year survival of less than 10% [1, 2]. RCC can be divided into three major subtypes with clear cell RCC (70¨C80%) being the prominent one. Most patients with clear cell RCC carry an inactivated von Hippel Lindau (VHL) tumor suppressor gene. The inactivation of this gene causes an upregulation of several survival and proangiogenic factors such as transforming growth factor-alpha (TGF- ) and vascular endothelial growth factor (VEGF). Apart from clear cell RCC, papillary (10¨C15%) and chromophobe RCC (5%) are histological subtypes of RCC. These subtypes can be caused, for example, by somatic mutations activating the tyrosine kinase of the cell surface receptor c-MET. The primary treatment strategy for renal cancer is surgery [3]. Metastatic RCC seems to be resistant to other conventional therapy regimens such as chemotherapy, hormone therapy, or radiotherapy [2, 4]. Until the recent evolution of targeted therapies, interleukin-2 (IL-2) combined with interferon-
%U http://www.hindawi.com/journals/jir/2012/473245/