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Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma
| Content Provider | Semantic Scholar |
|---|---|
| Author | Tsuchiya, Norihiko Yoshikawa, Toshiaki Fujinami, Norihiro Saito, Kazuki Mizuno, Shoichi Sawada, Yu Endo, Itaru Nakatsura, Tetsuya |
| Copyright Year | 2017 |
| Abstract | We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination. The secondary endpoints were clinical and biologic outcomes. We demonstrated that the present vaccine induced GPC3 peptide-specific cytotoxic T lymphocytes (CTLs), which were found to infiltrate into the tumor. Moreover, we established GPC3 peptide-specific CTL clones from a biopsy specimen: these cells exhibited GPC3 peptide-specific cytokine secretion and cell cytotoxicity. The plasma GPC3 level tended to decrease temporarily at least once during the follow-up period. The GPC3-specific CTL frequency after vaccination was correlated with overall survival. The degree of skin reactions at the injection site correlated with the GPC3 peptide-specific CTLs. Furthermore, we sequenced the T cell receptors (TCRs) of tumor-infiltrating lymphocyte (TIL) clones, and confirmed the existence of this TCR repertoire in both tumor tissue and PBMCs. In response to these data, we are developing TCR-engineered T cell therapy using TCR sequences obtained from GPC3 peptide-specific CTL clones for improved efficacy in patients with advanced HCC. |
| Starting Page | 232 |
| Ending Page | 250 |
| Page Count | 19 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 29123959v1 |
| Alternate Webpage(s) | https://doi.org/10.1080/2162402X.2017.1346764 |
| DOI | 10.1080/2162402x.2017.1346764 |
| Journal | Oncoimmunology |
| Volume Number | 6 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Biological Factors Biomarkers, Tumor Biopsy Specimen CDISC SEND Biospecimens Terminology Chronic Lymphocytic Leukemia Cytotoxic T-Lymphocytes Follow-Up Report Helper-Inducer T-Lymphocyte Infiltration Liver carcinoma Lymphocytes, Tumor-Infiltrating Neoplasms Overall Survival Patients Receptors, Cell Surface T-cell receptor complex location Vaccines, Peptide autologous Epstein-Barr virus-specific cytotoxic T lymphocytes (cell) cytokine glypican 3 tumor tissue |
| Content Type | Text |
| Resource Type | Article |
