Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients.
The prognosis of patients with advanced pancreatic cancer is extremely poor and there are only a few standard treatments. Here, we report the results of a Phase I clinical trial to investigate the safety, immunostimulatory effects, and antineoplastic activity of a multi-target vaccine composed of four distinct peptides derived from cancer-testis (CT) antigens and vascular endothelial growth factor receptors (VEGFRs). Nine patients with unresectable, advanced pancreatic cancer who were refractory to standard chemotherapy were enrolled. Each patient was vaccinated with HLA-A*2402-restricted peptides derived from the CT antigens kinesin family member 20A (KIF20A) and cell division cycle-associated 1 (CDCA1) as well as from VEGFR1 and VEGFR2 subcutaneously once a week, and disease progression was evaluated up to 6 mo later. Adverse events were assessed using the Common Terminology Criteria for Adverse Events v. 3.0. Immunological responses were monitored by ELISPOT assays and flow cytometry based on peptide-specific dextramers. The clinical outcomes that were measured were tumor response, progression-free survival (PFS) and overall survival (OS). In general, the multi-peptide vaccine was well-tolerated, and no grade 3 or 4 adverse events were observed upon vaccination. Peptide-specific T-cell responses were detected in all 9 patients, and clinical benefits were observed in four of them. Median PFS and OS were 90 and 207 d, respectively. The elicitation of multiple and robust peptide-specific T-cell responses as well as the status of host lymphocytes may be useful prognostic factors among patients with advanced pancreatic cancer treated with peptide-based anticancer vaccines.
Department of Gastroenterological Surgery; Tokyo Women's Medical University; Tokyo, Japan.
Ryuji
R
Okuyama
Department of Gastroenterological Surgery; Tokyo Women's Medical University; Tokyo, Japan ; Institute of Advanced Biomedical Engineering and Science; Tokyo Women's Medical University; Tokyo, Japan.
Atsushi
A
Aruga
Department of Gastroenterological Surgery; Tokyo Women's Medical University; Tokyo, Japan.
Takashi
T
Hatori
Department of Immunology; Juntendo School of Medicine; Tokyo, Japan.
Kazuyoshi
K
Takeda
Department of Gastroenterological Surgery; Tokyo Women's Medical University; Tokyo, Japan.
Masakazu
M
Yamamoto
VEGFR; cancer-testis antigens; clinical trial; immunotherapy; multi-target vaccine; pancreatic cancer; peptide