Multi-peptide immunotherapeutic vaccine for renal cell carcinoma: getting the troops all worked up

These are exciting times in the development of new immunotherapeutic strategies for cancer therapy. In particular, synthetic peptide-based vaccines, aiming at the induction of T-cell mediated anti-tumor immunity, hold immense promise for prevention and therapy of malignant diseases. Synthetic peptides are easily produced, are chemically stable, easily deliverable, free of infectious contaminants and devoid of oncogenic potential. Importantly, the simplicity of producing clinical grade peptides allows for rapid changes in the design of peptide vaccines and, therefore, rapid translation into phase I/ II trials in humans patients. Some clinical trials with therapeutic peptide vaccines so far are promising; a number of cancer patients exhibit immune responses against their tumor antigens and, to some extent, tumor regression (1,2). However, in many advanced cancer patients, peptide-based experimental therapy has shown limited benefit. Most encouragement for the immunotherapy community to pursue similar lines of therapeutic approach has come from cases where T cell responses against a tumor associated antigen (TAA) are induced by immunization. Unfortunately, while tumors expressing the immunized antigen may be destroyed, tumors that have lost expression of the antigen (or MHC) will remain untouched. The reason for such tumor escape is probably because tumor cells undergo antigenic variation and thereby avoid recognition and elimination by the immune system. Furthermore, antigen negative tumor variants will be positively selected upon the pressure of tumor destroying T cells. Thus, current immunotherapeutic strategies have evolved to include immunizations not only with one or two but with a number of different antigens simultaneously in order to circumvent the issue of tumor escape. Walter et al. have used a similar approach to develop a multi-epitope cancer vaccine-IMA901. Their study, published in Nature Medicine (3), describes a systematic, multicenter Phase I/II clinical trial set up to test the therapeutic potential of a multi-epitope vaccine-IMA901-in advanced renal cell cancer (RCC) patients. The overarching goal of their study was to develop an effective immunotherapeutic peptide vaccine consisting of multiple tumor-derived antigens in order to induce a broad and specific T cell-mediated immune response against various cancer cells. For a tumor-antigen derived peptide vaccine to be successful as a cancer immunotherapeutic, it is essential for the vaccine to prime cytotoxic CD8 + T cells in vivo, especially in the case of those cancers for which only a few tumor antigens have been defined so far. The authors address several key challenges involved in designing such a T cell response inducing …