This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV.
Seventy patients with metastatic castration-resistant prostate cancer were randomly assigned (1:1) to receive PPV plus oral low-dose CPA (50 mg/day), or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 pooled peptides according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL) and immunoglobulin G responses were measured before and after PPV. The incidence of grade 3 or 4 hematologic adverse events was higher in the PPV plus CPA arm than in the PPV alone arm. Decrease in Treg and increase in MDSC were more pronounced in PPV plus CPA treatment than in PPV alone (p = 0. 036 and p = 0. 048, respectively). There was no correlation between the changes in Treg or MDSC and CTL response. There was no difference in positive immune responses between the two arms, although overall survival in patients with positive immune responses was longer than in those with negative immune responses (p = 0. 001). Significant differences in neither progression-free survival nor overall survival were observed between the two arms. Low-dose CPA showed no change in the antitumor effect of PPV, possibly due to the simultaneous decrease in Treg and increase in MDSC, in patients under PPV.
Cancer immunology, immunotherapy : CII. 2016 Jan 04 [Epub ahead of print]
Masanori Noguchi, Fukuko Moriya, Noriko Koga, Satoko Matsueda, Tetsuro Sasada, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh
Division of Clinical Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. Department of Pathology, Kurume University School of Medicine, Kurume, Japan. , Division of Clinical Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. , Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan. , Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan. , Division of Cancer Vaccines, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. , Bio-statistics Center, Kurume University School of Medicine, Kurume, Japan. , Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan.