Cancer peptide vaccine to suppress postoperative recurrence in esophageal SCC patients with induction of antigen-specific CD8+ T cell.

Abstract

e14635 Background: This is a following report of the exploratory phase II study of adjuvant peptide vaccine for thoracic esophageal squamous cell carcinoma (TESCC) (abstract #3087 in ASCO2016), focusing on an association of immunological responses with clinical outcomes. Three HLA-A-24-restricted epitope peptides derived from cancer-testis antigens, up-regulated lung cancer 10 (URLC10), cell division cycle associated 1 (CDCA1) and KH domain-containing protein overexpressed in cancer 1 (KOC1), were used in this study. Methods: TESCC patients who underwent neoadjuvant therapy followed by curative resection (Dec./2009 to Sep./2014) and were found LN metastasis were enrolled. One mg each of three peptides mixed with Montanide was injected to patients with HLA-A*2402 20 times in a 6-months period. No other adjuvant therapy was given until recurrence occurred. Primary endpoint is relapse-free survival (RFS). Immunological responses were examined by ELISPOT assay and immunohistochemistry (IHC). Results: 33 patients were enrolled in the vaccine group (VG) and 30 with non-HLA-A*2402 were used as controls (CG). There was no significant difference in clinical backgrounds between the two groups. 5-year RFS in the VG was 44.6% while that in the CG group was 31.6% (p = 0.207); patients who showed CD8+ CTL induction to multiple peptides tend to show better RFS rate [3/2/1 peptides = 69.0(n = 20)/46.8(n = 11)/0%(n = 2), respectively]. Five-year esophageal cancer-specific survival (ECSS) were 58.4% in the VG compared with 35.4% in the CG (p = 0.156); 90.0% (n = 11) vs. 50.0% (n = 15) and 43.8% (n = 22) vs. 24.0%(n = 15) in pN1 and pN2-3 groups, respectively. Regarding the CD8+ positivity, ECSS was improved only in the negative group (56.6% in VG vs. 26.7% in CG). Classification by T cell positivity and PD-L1 expression [type I(+/+), II(-/-), III(-/+) and IV(+/-)] showed 5-year ECSS to be 100%(n = 3), 66.4%(n = 19), 20.0%(n = 5) and 44.4%(n = 6). Conclusions: Our cancer peptide vaccines induced the antigen-specific CD8+ T cell highly and efficiently, and suppressed recurrence with the strong immune responses. Clinical trial information: UMIN000003557.