AGS-003 combined with sunitinib for the precision treatment of metastatic renal cell carcinoma

ABSTRACT

Introduction: Unselective approaches of immunotherapy in metastatic renal cell cancer (mRCC) have been largely abandoned over the past decade. Despite the established clinical benefit of tyrosine kinase inhibitors for mRCC and the recent successful implementation of immune check-point inhibition, specific immunotherapy may additionally contribute to anti-cancer immune response with good tolerability and long-term clinical benefit.

Areas covered: AGS-003 represents an approach of specific immunotherapy using a dendritic cell-based vaccine based on monocyte derived dendritic cells, which are co-electroporated with individual antigen coding amplified tumor RNA and synthetic CD40L RNA. After successful clinical phase I and II trials, current evaluation of AGS-003 in mRCC in combination with sunintib is under way in a phase III clinical trial and results are awaited.

Expert commentary: Initial results from clinical evaluation of AGS-003 are promising also based on the underlying mechanistic rationale. Toxicity profiles in combinatory regimens are mainly attributed to the side effects of the respective drugs. Apart from further awaited results of the oncologic efficacy of AGS-003 in mRCC, it will be of interest how the preparation of the compound ex vivo and issues related to cost and logistics will affect a potential clinical application of AGS-003 in the daily routine practice.

KEYWORDS:

• Renal cell carcinoma
• immunotherapy
• vaccination
• AGS-003
• TKI
• dendritic cell
• metastasis
• immune system​​

Declaration of Interest

J Bedke: consultancies, honoraria or study participation from Bayer, BMS, Eisai, GSK, Immatics, MSD, Nektar, Novartis, Pfizer and Roche. A Stenzl: consultancies, honoraria or study participation from Bayer, BMS, Immatics, Novartis, Pfizer and Roche. 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 apart from those disclosed.

Additional information

Funding

S Rausch is supported by a Ferdinand-Eisenberger-Grant of the German Society of Urology (RaS01/FE-14). J Bedke is supported by a grant by the Deutsche Forschungsgemeinschaft (SFB685, C5).