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.
Keywords: 5-FU, 5 fluorouracil; AE, Adverse event; CTL, Cytotoxic T-lymphocyte; CY, Cyclophosphamide; Cancer vaccine; DC, Dendritic cell; DCR, Disease control rate; ECG, Electrocardiogram; ELISpot, Enzyme-linked immunospot assay; FDA, Food and Drug Administration; GM-CSF; HBV, Hepatitis B virus; HLA, Human leukocyte antigen; IFN, Interferon; IL, Interleukin; IMA901; MDSC, Myeloid-derived suppressor cells; MHC, Major histocompatibility complex; MSKCC, Memorial Sloan Kettering Cancer Center; NCI-CTC, National Cancer Institute-Common Toxicity Criteria; OS, Overall survival; PD, Progressive disease; PFS, Progression-free survival; PK, Pharmacokinetic; PR, Partial response; RCC, Renal cell carcinoma; RECIST, Response Evaluation Criteria in Solid Tumors; SAE, Serious adverse event; SD, Stable disease; TKI, Tyrosine-kinase inhibitors; TNF, Tumor necrosis factor; TUMAP, Tumor-associated peptides; Tregs, Regulatory T-cells; VEGF, Vascular endothelial growth factor; ccRCC, Clear cell renal cell carcinoma; checkpoint inhibitor; cyclophosphamide; i.d., intradermal; immunotherapy; intradermally; kidney cancer; mRNA, Messenger ribonucleic acid; mTOR, Mammalian target of rapamycin; mg, Milligram; n, Number; renal cell carcinoma; s.c., subcutaneous, subcutaneously; tumor-associated peptides; vaccination; μg, Microgram.