Vaccine therapy in patients with renal cell carcinoma

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.