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.