Immunotherapeutic strategies for the treatment of renal cell carcinoma: Where will we go?

ABSTRACT

Introduction: Historically, renal cell carcinoma (RCC) is considered a chemotherapy-resistant tumor. The cornerstone of systemic therapy included mammalian target of rapamycin (mTOR) inhibitors, endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Currently, a new era is enteres with promising immunotherapeutic treatments, which are becoming commercially available.

Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy – IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules. We will also discuss their mechanism of action and toxicity, the importance of developing new patient selection algorithms (immunoprofiling, guidelines updates) and new biomarkers such as PD-1 expression.

Expert commentary: Immunotherapy shows promise, and the current tools used in clinical practice, including guidelines, staging-classification and algorithms should be revised and adapted to the new immunotherapeutic drugs. Although immunotherapy in RCC show promising results, more research is needed in parallel to discover biomarkers that enable the prediction of a treatment response and therefore lead to better patient selection.

KEYWORDS:

• Renal cell carcinoma
• immunotherapy
• checkpoint inhibitors
• programmed death receptor 1
• combination therapy
• tumor vaccine
• nivolumab
• pembrolizumab
• atezolizumab
• cabozantinib

Acknowledgments

The authors thank Dr. Daniel Wood for assistance in grammar revision and for critical review of the manuscript.

Declaration of interest

JB: consultancies, honoraria or study participation from Bayer, BMS, GSK, Immatics, Nektar, Novartis, Pfizer and Roche. SK: consultancies, honoraria or study participation: BMS, Bayer, Novartis, Pfizer. TT: travel grant: Bayer AS: consultancies, honoraria or study participation from Bayer, BMS, Immatics, Novartis, Pfizer and Roche. SR is supported by a Ferdinand-Eisenberger Grant of the German society of Urology (RaS1/FE-14) and Jens Bedke by a grant of the Deutsche Forschungsgemeinschaft (DFG, SFB685, C5). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This article was not funded.