Long-term vaccination with multiple peptides derived from cancer-testis antigens can maintain a specific T-cell response and achieve disease stability in advanced biliary tract cancer
Mené sur 9 patients atteints d'un cancer des voies biliaires de stade avancé et réfractaire aux traitements de référence, cet essai de phase I évalue, du point de vue de la réponse tumorale, de la survie sans progression et de la survie globale, un vaccin à base de quatre peptides
Purpose: The prognosis of patients with advanced biliary tract cancer is extremely poor and there are only a few standard treatments. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with four peptides derived from cancer-testis antigens, with a focus on their fluctuations during long-term vaccination until the disease had progressed. Experimental Design: Nine patients with advanced biliary tract cancer who had unresectable tumors and were refractory to standard chemotherapy were enrolled. HLA-A*2402-restricted epitope peptides, lymphocyte antigen 6 complex locus K, TTK protein kinase, insulin-like growth factor (IGF)-II mRNA binding protein 3 and DEP domain containing 1 were vaccinated subcutaneously once a week and continued until disease progression. The adverse events were assessed by Common Terminology Criteria for Adverse Events and the immune response was monitored by an enzyme-linked immunospot assay or by flow cytometry. The clinical effects observed were tumor response, progression-free survival (PFS) and overall survival (OS). Results: Four-peptide vaccination was well-tolerated. No grade 3 or 4 adverse events were observed. Peptide-specific T cell immune responses were observed in 7 of 9 patients and clinical responses were observed in 6 of 9 patients. The median PFS and OS were 156 and 380 days. The injection site reaction and CTL induction seemed to be prognostic factors of both PFS and OS. Conclusions: Four-peptide vaccination was well-tolerated and appeared to provide some clinical benefit to some patients. These immunologic and clinical responses were maintained over the long-term through continuous vaccinations.