Further insight into AE37 peptide vaccination in prostate cancer

Cancer peptide vaccination, as an immunotherapeutic approach against solid tumors, is currently employed in several clinical research protocols. The underlying mechanism of peptide-based vaccines involves the generation of a T-cell immune response against tumor or enhancement of an endogenous antitumor immunity pre-existing in the host [1]. Although the rationale of cancer vaccination studies seems to be promising, therapeutic efficacy is rather limited [2,3]. One reason that could account for that is the inappropriate clinical trial design and patient selection, rather than the vaccine itself [3]. It is important to underline that the antitumor immune response is influenced by the respective immunological status and tumor-cell characteristics, thus implying heterogeneity among patients [4]. In respect to this, T-cell responses against certain peptides, including those derived from tumors, are mediated by specific human leukocyte antigen (HLA) molecules, therefore, the HLA polymorphism is another factor reflecting this variation in patients’ immunological response [5]. Given that, patients’ selection in vaccination studies requires careful consideration, so as to achieve therapeutic efficacy. According to recent reports, pre-existing host immunity is essential in order to gain a therapeutic benefit, in the context of peptide cancer vaccines [2,6]. More specifically, patients with a pre-existing immunity to the vaccine antigen can develop fast and robust immune responses, upon vaccination. In addition, since pre-existing immunity against peptides integrated in the vaccine formulation, has been shown to be a predictive biomarker of response and therapeutic benefit, it should be used to select patients who are likely to respond to the vaccine [7]. On the contrary, delayed and insufficient immune responses are observed in patients with no immunological memory to the vaccine antigen and especially those with advanced cancer, characterized also by high immunosuppresion levels due to disease progression [8]. Considering the heterogeneity among individuals along with the role of pre-existing immunity prior to vaccination, a more personalized approach in peptide-based vaccination studies could result in better responses and further contribute to the development of effective cancer vaccines. In line with this, the HLA phenotype and levels of pre-existing immunity could be employed in clinical trials in order to identify cancer patients that could benefit from a specific peptide vaccine. In this respect, a recent study from our group showed that prostate cancer patients vaccinated with the Ii-key hybrid HER2 peptide [9], exhibit longer progression-free survival when they have increased levels of pre-existing immunity to the respective native HER2 peptide (AE36). In this study, additionally to enzyme-linked immunosorbent spot IFN-γ, we used the local reaction (LR) at the inoculation site of the first vaccine (500 μg peptide + 125 μg granulocyte-macrophage colony stimulating factor) (LR1) as an approach for assessing pre-existing immunity, besides the generally Further insight into AE37 peptide vaccination in prostate cancer