Personalized Kampo Medicine Facilitated Both Cytotoxic T Lymphocyte Response and Clinical Benefits Induced by Personalized Peptide Vaccination for Advanced Esophageal Cancer.

Daisuke Muroya,Rin Yamaguchi,Koji Okuda,Shinjiro Sakamoto,Masayasu Naito,Akira Yamada,Kyogo Itoh,Shigeru Yutani,Michi Morita,Shigeki Shichijo

doi:10.1155/2016/5929525

Abstract

We retrospectively evaluated if personalized Kampo medicine (PKM) could facilitate CTL responses and clinical benefits induced by personalized peptide vaccination (PPV), in which HLA-matched vaccines were selected and administered based on the preexisting host immunity, for advanced esophageal cancer (aEC) patients. Among 34 aEC patients entered in the clinical study, 23 patients received PKM and PPV without (n = 12) or with chemotherapy (n = 11), while the remaining 11 patients did not receive PKM but received PPV without (n = 6) or with chemotherapy (n = 5), respectively. Incidence of adverse events was significantly lower or higher in PKM and PPV arm (n = 23) or PPV and chemotherapy arm (n = 16) as compared to that of the counter arm (n = 11 or 18), respectively. Postvaccination PBMCs from the patients undergoing PKM and PPV showed significantly higher CTL responses as compared to the counter arm. The median progression-free survival (PFS) or median survival time (MST) of 34 patients was 2.9 or 7.6 months, respectively. The combination therapy in PPV and PKM arm, but not that in PPV and chemotherapy arm, significantly (P = 0.02) prolonged MST. These results could warrant a next step of prospective clinical study of PKM and PPV for aEC patients.

Highlights

The majority of esophageal cancer patients present with unresectable or metastatic disease at the time of diagnosis, and recurrences are common in these advanced esophageal cancer patients [1,2,3,4]
To explore a new treatment modality for advanced esophageal cancer (aEC) patients, we retrospectively evaluated in this study if the KM prescribed with a personalized manner (termed as personalized Kampo medicine (PKM)) facilitated CTL responses and clinical benefits induced by peptide vaccination (PPV) for aEC patients
Because the original tumors of each patient under PPV were not available, we examined the expression of 15 different mother antigens in resected tumors or biopsy samples from nonvaccinated squamous cell carcinoma of the esophagus (n = 10)

Summary

Introduction

The majority of esophageal cancer patients present with unresectable or metastatic disease at the time of diagnosis, and recurrences are common in these advanced esophageal cancer (aEC) patients [1,2,3,4]. Palliative treatment is the only option for controlling cancer-related symptoms in these patients. Newer therapeutic approaches for aEC should be developed, and immunotherapy would be a promising candidate. PPV could provide both CTL responses and clinical benefits for advanced bladder cancers and colorectal cancers as reported [5,6,7]. PPV by itself could not generally provide either CTL boosting or clinical benefits for the majority of advancer cancer patients except for those two types

Methods

Results

Discussion

Conclusion