Abstract 5578: Phase 1 study of XAGE1 peptide vaccine in patients with lung adenocarcinoma
Authors: Oka Mikio , Kurose Koji , Yasogawa Naoya , Yamaoka Takaaki , Ohue Yoshihiro , Oga Toru 
Published: September 2020

Abstract
Background: Lung adenocarcinomas show the highest proportion of approximately 70% among histologic types of non-small-cell lung cancer (NSCLC). Generally, lung adenocarcinomas have many passenger mutations in smokers and driver mutations such as EGFR and EML-ALK gene in non- or light smokers. On the other hand, NSCLC simultaneously expresses many cancer-testis (CT) antigens, which are expressed in cancer and normal testis tissues only. We previously reported that XAGE1 (81 amino acids) of a CT antigen is specifically expressed in approximately 40% to 60% of lung adenocarcinomas, and that it elicits spontaneous T cell and humoral immune responses in almost half of patients with XAGE1. In addition, lung adenocarcinomas with XAGE1 antigen and antibody (Ab) showed prolonged survival as compared with those of XAGE1-Ab-negative patients. Thus, XAGE1 is a major immunodominant antigen and play an important role in the immune surveillance of lung adenocarcinomas. Then, we for the first time conducted a phase 1 study of XAGE1 peptide vaccines in patients with lung adenocarcinoma.
Patients and Methods: Two long-peptide vaccines of SLP1 and SLP2 were synthesized, and SLP1 and SLP2 were composed with 25-mer of XAGE1 peptide 6N~32Q and 44I~68H, respectively. The two peptide epitopes were considered to be recognized in both CD4 and CD8 T cell. The two peptide vaccines mixed with 0.2 KE Picibanil OK-432 of adjuvant and 1.25 ml Montanide ISA-51 were administered in advanced lung adenocarcinoma patients with XAGE1 antigen or Ab. Four doses of 500 micro-gram (level-1), 1 mg (level-2), and 2 mg (level-3) each were subcutaneously administered every two weeks. Primary and secondary endpoint of this study were safety and XAGE1-specific immune responses, respectively.
Results: A total of ten patients was enrolled into this study, which was consisted of each three in level-1 and level-3 and four in level-2. The study was completed in 7 out of 10 patients, and three were dropped due to disease progression. Thirty-four adverse events related to vaccines were observed but not serious (grade 1 or 2); 9 skin induration, 6 fever, 4 local pain at injection, and so on. Before the vaccination, seven patients were positive for XAGE1-Ab, and three were negative. After the vaccination, the Ab titers were increased in five of seven XAGE1-Ab-positive patients, and one of three XAGE1-Ab-negative patients showed seropositive. Clinically, tumor marker CEA was decreased in two patients after the vaccination. On the other hand, CD4 T cells were isolated from one patient 12 weeks after the vaccination, and were stimulated in vitro by SLP1, SLP2, and the mixture with SLP1 and SLP2. The highest level of IFN-gamma secretion was observed in the mixture than those in SLP1 and SLP2 alone.
Conclusions: This study shows that our XAGE1 peptide vaccine was well tolerated and elicited humoral and CD4 T cell responses in immunized patients.
Citation Format: Mikio Oka, Koji Kurose, Naoya Yasogawa, Takaaki Yamaoka, Yoshihiro Ohue, Toru Oga. Phase 1 study of XAGE1 peptide vaccine in patients with lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5578.