Introduction
Recent advances in pediatric multidisciplinary cancer therapy have resulted in long-term survival and full recovery in most patients.1,2 However, this impressive advancement is associated with late adverse effects owing to repeated intense treatments needed to achieve these results. One of the effects is the suppression of immune responses, which might in turn result in early recurrence3,4 or the development of secondary cancers. We developed a new approach for cancer immunotherapy, i.e., a personalized peptide vaccine (PPV), wherein peptides are selected from 31 different peptide candidates for individual patients on the basis of their secondary immune responses5-7. The PPV resulted in a longer overall survival (OS) in some patients with advanced adult cancers, as observed in phase II studies.8,9 Humoral responses against these 31 peptides—encoded by 15 different tumor-associated antigens—are detectable in healthy donors and cancer patients, and these levels were biomarkers for OS in not only vaccinated patients but also unvaccinated patients with advanced cancer.10,11 However, little is known about the immunological features of patients with refractory childhood cancer considering the tumor immunology, partly owing to the lack of an affordable assay system to measure the preexisting antitumor immunity. Accordingly, we conducted the current early phase II clinical study for patients with refractory childhood cancer to evaluate the possible application of the PPV as a new immunotherapy modality.