IMA901 is the first therapeutic vaccine for renal cell cancer (RCC). It contains multiple tumor-associated peptides (TUMAPs) that are naturally present in human cancers.
In a phase I/II study, we treated a total of 10 Japanese patients with advanced RCC who were human leukocyte antigen A (HLA-A)*02 +. Vaccination involved i.d. injection of GM-CSF (75 μg), followed within 15-30 min by i.d. injection of IMA901 (containing 413 μg of each peptide). No treatment with either anticancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were scheduled to receive 7 vaccinations during the first 5 weeks of treatment (induction period), followed by 10 further vaccinations at 3-week intervals for up to 30 weeks (maintenance period). The primary endpoints were safety and tolerability, while the secondary endpoints were PFS, OS, and immunogenicity.
There were no treatment-related serious adverse events or deaths during the study period. When the response was assessed after 4 months, 10% of patients showed a partial response, 80% had stable disease, and 10% had progressive disease. Among patients in whom the T-cell response was analyzed, five patients showed a vaccine-induced T-cell response against at least one HLA class I-restricted TUMAP and two patients had T-cell responses to multiple TUMAPs. PFS was 5.5 months and OS was 18 months.
This study demonstrated the safety and tolerability of IMA901 vaccine in Japanese RCC patients, and also showed that vaccination elicited an immune response.

Despite a major improvement in the treatment of advanced kidney cancer by the recent introduction of targeted agents such as multi-kinase inhibitors, long-term benefits are still limited and a significant unmet medical need remains for this disease. Cancer immunotherapy has shown its potential by the induction of long-lasting responses in a small subset of patients, however, the unspecific immune interventions with (high dose) cytokines used so far are associated with significant side effects. Specific cancer immunotherapy may circumvent these problems by attacking tumor cells while sparing normal tissue with the use of multi-peptide vaccination being one of the most promising strategies. We here summarize the clinical and translational data from phase I and II trials investigating IMA901. Significant associations of clinical benefit with detectable T cell responses against the IMA901 peptides and encouraging survival data in treated patients has prompted the start of a randomized, controlled phase III trial in 1st line advanced RCC with survival results expected toward the end of 2015. Potential combination strategies with the recently discovered so-called checkpoint inhibitors are also discussed.

The promising option of immunotherapy for metastatic renal cell carcinoma has evolved from rather unspecific approaches to a specific activation of an anti-tumor T-cell response. The latest step is a synthetic peptide vaccine called IMA901, which demonstrated a clear association between a provoked T-cell response and a prolonged overall survival. The results of IMA901 for the treatment of metastatic renal cell carcinoma are discussed together with new approaches to immunotherapy, such as local and systemic immunomodulation with adjuvants, checkpoint inhibitors, classical chemotherapeutics, such as cyclophosphamide or tyrosine kinase inhibitors. The capability of theses substances to modulate leukocytes subsets, such as myeloid-derived suppressor cells, Tregs or Th17 cells, are outlined together with the possibility to combine them with tumor vaccination strategies to achieve a higher cancer specificity and immunogenicity.