Immunotherapy of renal cell carcinoma

Abstract

Targeted therapy has been the standard of care for the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), antibodies to circulating VEGF receptor (bevacizumab) and m-TOR inhibitors (temsirolimus, everolimus). New immune-based therapies are emerging as a promising treatment for mRCC. Immune checkpoint blockade has shown clinically significant antitumor response. Monoclonal antibodies against immune checkpoint blockade molecules including PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) have become a major focus in the immune-based therapy since it has been reported that they have impressive antitumor effects. The most studied inhibitors in the PD-1 pathway are: nivolumab, pembrolizumab and atezolizumab. Based on the results of the phase III clinical trial (CheckMate025) nivolumab, humanized monoclonal IgG4 antibody against PD-1, is the only agent that is approved by the FDA for the second-line treatment of mRCC. Ipilimumab is the first-in-class immunotherapeutic for blockade of CTLA-4. The immunotherapy combinations have demonstrated promising results in a randomized trials. The use of cancer treatment vaccines is another approach to immunotherapy and will be systematically evaluated in the future. Immunotherapy has demonstrated great clinical potential and it represents crucial component of mRCC treatment. Developing immunotherapy to the point of clinical utility presents a number of issue and challenges, and more rigorous studies are needed.