Elsevier

European Urology

Volume 55, Issue 6, June 2009, Pages 1333-1344
European Urology

Review – Kidney Cancer
Vaccine Therapy in Patients with Renal Cell Carcinoma

https://doi.org/10.1016/j.eururo.2009.01.043Get rights and content

Abstract

Context

Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans. Although immunotherapy is currently much less used than in the past, it remains an important option that warrants further exploration.

Objective

To examine the current status of vaccine therapy for RCC and to provide information on relevant clinical studies.

Evidence acquisition

We reviewed recent literature on Medline (2003–2008, using the keywords renal cell carcinoma, cancer vaccines, active immunotherapy, and dendritic cells). Subsequent references were identified from reference list of retrieved articles. Quality assessment included prospective phase 1–3 trials and critical evaluations with low numbers of patients.

Evidence synthesis

Therapeutic vaccines can be divided in autologous tumour cell–based vaccines, genetically modified tumour cell–based and dendritic cell (DC)–based vaccines, and peptide-based vaccines. To date, only two randomised, adjuvant, phase 3 studies investigating RCC vaccines have been published. Autologous tumour cell vaccine (Reniale) improved the 5-yr progression-free survival (PFS) for high-risk nonmetastatic RCC patients at all tumour stages when administered after nephrectomy. The benefit was clearer in the T3 group. A per-protocol analysis revealed a statistically significant PFS and overall survival (OS) in favour of the vaccine. Autologous tumour-derived heat shock protein peptide complex (HSPPC-96; vitespen) could not significantly improve recurrence-free survival in RCC patients at high risk for recurrence after nephrectomy, but did so in intermediate risk patients. DC vaccination in metastatic RCC (mRCC) patients is safe and can induce antigen-specific immune response and obtain tumour regression in a subset of patients.

Conclusions

RCC vaccines have much less toxicity than other current therapies and remain an important area for further research. Reniale has shown significant benefit as an adjuvant RCC vaccine. Vitespen seems promising as an adjuvant treatment in earlier stage disease. A possible area of research is the use of RCC vaccines with immune-enhancing or antiangiogenic agents in the adjuvant setting.

Introduction

Renal cell carcinoma (RCC) accounts for 2–3% of all adult cancers. There is a general European annual increase in incidence of around 2%, except in Denmark and Sweden. Approximately 20–30% of patients present with metastatic disease [1]. Although surgery is the primary curative therapy for patients with localised RCC, the prognosis for patients with advanced metastatic disease is poor, with a 5-yr survival rate of <10% [2]. Until recently, the standard therapy for metastatic RCC (mRCC) has been cytokine-based immunotherapy with interleukin-2 (IL-2) and/or interferon alfa (IFN-α), with only few durable complete remissions. Therefore, new therapeutic agents with more effective antitumour activity are needed [3]. Recently, the antiangiogenic agents sunitinib, sorafenib, temsirolimus, and bevacizumab plus interferon were licensed in Europe for the treatment of mRCC [4].

Because RCC is one of the most immunoresponsive cancers in humans, immunotherapy remains a basis of promising treatment strategies. Nonspecific stimulations via cytokines, passive specific immunotherapy with antibodies, and active specific immunotherapy seem to be suitable options for RCC. The last category is the subject of this review.

The goal of developing curative RCC vaccines is to stimulate the immune system to recognise and to destroy existing tumour cells. RCC vaccines are explored in the metastatic and adjuvant setting. To date, they are only clinically effective in a minority of patients and are still considered experimental. This review provides an overview of the current knowledge of vaccine therapy for RCC and information on relevant clinical studies.

Section snippets

Evidence acquisition

A review was conducted of the recent literature regarding vaccine therapy for RCC. The following medical subject heading (MeSH) terms were identified in PubMed: Carcinoma, Renal Cell; Cancer Vaccines; Immunotherapy, Active; and Dendritic Cells. The search for the last three terms was performed by using the clinical queries using research methodology filters for the category therapy (based on the work of Haynes et al [5]). They were then linked with the option “OR” and combined with Carcinoma,

Evidence synthesis

The search retrieved 96 abstracts; 54 papers were relevant to use.

Conclusions

Despite the limited clinical efficacy of most of the therapeutic vaccines in RCC studies to date and their often small number of patients and nonstandardised methodology, there is still interest for the use of vaccines that have much less toxicity than other current therapies for RCC. One of the major obstacles for development of effective RCC vaccines has been the lack of TAAs. The discovery of new TAAs or immunostimulatory peptides and increasing insight in basic immunology and molecular

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