Targeted therapy in renal cell carcinoma: moving from molecular agents to specific immunotherapy

Jens Bedke,Stefan Stevanović,Harpreet Singh-Jasuja,Cécile Gouttefangeas,Arnulf Stenzl,Carl-Ludwig Behnes

doi:10.1007/s00345-013-1033-3

Abstract

Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. After moving treatment for mRCC to specific molecular agents with a well-defined mode of action, immunotherapy still needs this further development to increase its accuracy. Nowadays, an evolution from a rather non-specific cytokine treatment to sophisticated targeted approaches in specific immunotherapy led to a re-launch of immunotherapy in clinical studies. Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes. In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed.

Highlights

The observation of rare spontaneous tumor regressions in RCC has led to the early assumption that RCC is an immunogenic tumor [1]
Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes
Cell antigen processing leads to the display of such human leukocyte antigen (HLA)-restricted peptides derived from tumor-associated antigens (TAAs), known as tumor-associated peptides (TUMAPs)

Summary

Introduction

The observation of rare spontaneous tumor regressions in RCC has led to the early assumption that RCC is an immunogenic tumor [1]. It was observed that targeted agents do inhibit angiogenesis and tumor cell proliferation, and show immunomodulatory effects directing the immune system to a stronger anti-tumor response [15]. This immune therapy does not present a very well-defined mode of action and does not induce a specific T-cell response directed toward known tumor-associated antigens (TAAs).

Results

Conclusion