Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens

Kono Koji, Iinuma Hisae, Akutsu Yasunori, Tanaka Hiroaki, Hayashi Naoko, Uchikado Yasuto, Noguchi Tsuyoshi, Fujii Hideki, Okinaka Kota, Fukushima Ryoji, Matsubara Hisahiro, Ohira Masaichi, Baba Hideo, Natsugoe Shoji, Kitano Seigou, Takeda Kazuyoshi, Yoshida Koji, Tsunoda Takuya, Nakamura Yusuke

Description

Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK), lymphocyte antigen-6 complex locus K (LY6K), and insulin-like growth factor-II mRNA binding protein-3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, non-randomized phase II clinical trial. Patients and methods Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402 -positive (24(+)) and -negative (24(−)) groups. Results The OS in the 24 (+) group (n = 35) tended to be better than that in the 24(−) group (n = 25) (MST 4.6 vs. 2.6 month, respectively, p = 0.121), although the difference was not statistically significant. However, the PFS in the 24(+) group was significantly better than that in the 24(−) group ( p = 0.032). In the 24(+) group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. Conclusions The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. Trial registration ClinicalTrials.gov, number NCT00995358

Sujets

• Cancer vaccine
• Esophageal cancer
• Clinical trial
• CTL
• Peptide vaccine

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 10
• Langue: English

Extrait

Konoet al. Journal of Translational Medicine2012,10:141 http://www.translationalmedicine.com/content/10/1/141

R E S E A R C HOpen Access Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancertestis antigens 1,10* 23 45 6 Koji Kono, Hisae Iinuma , Yasunori Akutsu , Hiroaki Tanaka , Naoko Hayashi , Yasuto Uchikado , 7 12 23 4 Tsuyoshi Noguchi , Hideki Fujii , Kota Okinaka , Ryoji Fukushima , Hisahiro Matsubara , Masaichi Ohira , 5 67 89 9 Hideo Baba , Shoji Natsugoe , Seigou Kitano , Kazuyoshi Takeda , Koji Yoshida , Takuya Tsunodaand 9 Yusuke Nakamura

Abstract Background:Since a phase I clinical trial using three HLAA24binding peptides from TTK protein kinase (TTK), lymphocyte antigen6 complex locus K (LY6K), and insulinlike growth factorII mRNA binding protein3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, nonrandomized phase II clinical trial. Patients and methods:Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLAA type, and the HLA types were keyopened at the analysis point. Hence, the endpoints were set to evaluate differences betweenHLAA*2402positive (24(+)) and negative (24(−)) groups. Results:The OS in the 24 (+) group (n= 35)tended to be better than that in the 24(−= 25)(MST 4.6 vs.) group (n 2.6 month, respectively,palthough the difference was not statistically significant. However, the PFS in the= 0.121), 24(+) group was significantly better than that in the 24(−) group (p= 0.032).In the 24(+) group, ELISPOT assay indicated that the LY6K, TTK, and IMP3specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K, TTK, and IMP3specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. Conclusions:The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. Trial registration:ClinicalTrials.gov, number NCT00995358 Keywords:Cancer vaccine, Esophageal cancer, Phase II clinical trial, CTL, Peptide vaccine

* Correspondence: [e-mail] 1 First Department of Surgery, University of Yamanashi, Yamanashi, Japan 10 Department of Surgery, National University of Singapore, Level 8, NUHS Tower Block, NUHS 1E Kent Ridge Road, 119228, Singapore, Singapore Full list of author information is available at the end of the article

© 2012 Kono et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.