Multiple therapeutic peptide vaccines for patients with advanced gastric cancer

Fujiwara,Yoshiyuki; Okada,Kaoru; Omori,Takeshi; Sugimura,Keijiro; Miyata,Hiroshi; Ohue,Masayuki; Kobayashi,Shogo; Takahashi,Hidenori; Nakano,Hiroyuki; Mochizuki,Chie; Shimizu,Katsuji; Yano,Masahiko; Nakamura,Yusuke; Mori,Masaki; Doki,Yuichiro

doi:10.3892/ijo.2017.3955

Multiple therapeutic peptide vaccines for patients with advanced gastric cancer

Authors:
- Yoshiyuki Fujiwara
- Kaoru Okada
- Takeshi Omori
- Keijiro Sugimura
- Hiroshi Miyata
- Masayuki Ohue
- Shogo Kobayashi
- Hidenori Takahashi
- Hiroyuki Nakano
- Chie Mochizuki
- Katsuji Shimizu
- Masahiko Yano
- Yusuke Nakamura
- Masaki Mori
- Yuichiro Doki
View Affiliations

Affiliations: Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan, Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan, Department of Pharmacy, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan, Center for Personalized Therapeutics, The University of Chicago, Chicago, IL 60637, USA, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
Published online on: April 6, 2017 https://doi.org/10.3892/ijo.2017.3955
Pages: 1655-1662

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

We performed a clinical trial using HLA-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides for advanced gastric cancer (GC). Thirty-five GC patients who had shown resistance to the standard therapy were enrolled in this clinical trial using vaccinations with a mixture of multiple peptides derived from DEPDC1, URLC10, FoxM1, Kif20A and VEGFR1. The safety, the overall survival (OS), and the immunological responses based on an ELISPOT assay were determined to assess differences in patients who were HLA-A24-positive [24(+)] and HLA-A24-negative [24(-)]. No severe adverse effects were observed except for severe skin reactions in 4 patients. The differences in OS were not significant between patients who were 24(+) and 24(-). In the 24(+) group, patients who showed T cell responses specific to antigen peptides had a tendency towards better survival than those who showed no response, especially to the DEPDC1 peptide. The patients with local skin reactions had significantly better OS than the others. Peptide vaccine therapy was found to be safe and is expected to induce specific T cell responses in patients with advanced GC. The survival benefit of peptide vaccine monotherapy may not have been shown and further trials are needed to confirm these results.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Ajani JA, Fairweather J, Dumas P, Patt YZ, Pazdur R and Mansfield PF: Phase II study of Taxol in patients with advanced gastric carcinoma. Cancer J Sci Am. 4:269–274. 1998.PubMed/NCBI
3	Einzig AI, Neuberg D, Remick SC, Karp DD, O'Dwyer PJ, Stewart JA and Benson AB III: Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: The Eastern Cooperative Oncology Group (ECOG) results of protocol E1293. Med Oncol. 13:87–93. 1996. View Article : Google Scholar : PubMed/NCBI
4	Futatsuki K, Wakui A, Nakao I, Sakata Y, Kambe M, Shimada Y, Yoshino M, Taguchi T and Ogawa N: Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group. Gan To Kagaku Ryoho. 21:1033–1038. 1994.In Japanese. PubMed/NCBI
5	Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y and Taguchi T: Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer. 34:1715–1720. 1998. View Article : Google Scholar
6	Taguchi T, Tsukagoshi S, Furue H, Niitani H and Noda K: Phase I clinical study of oxaliplatin. Gan To Kagaku Ryoho. 25:1899–1907. 1998.In Japanese. PubMed/NCBI
7	Liu C, Sun Q, Hang X, Zhong B and Wang D: Multicenter phase II study of capecitabine plus oxaliplatin as a first-line therapy in Chinese patients with advanced gastric cancer. Anticancer Drugs. 19:825–831. 2008. View Article : Google Scholar : PubMed/NCBI
8	Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol. 9:215–221. 2008. View Article : Google Scholar : PubMed/NCBI
9	Japanese Gastric Cancer Association: Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 14:101–112. 2011. View Article : Google Scholar : PubMed/NCBI
10	Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al: ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomized controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar : PubMed/NCBI
11	Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, et al RAINBOW Study Group: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol. 15:1224–1235. 2014. View Article : Google Scholar : PubMed/NCBI
12	Boon T, De Plaen E, Lurquin C, Van den Eynde B, van der Bruggen P, Traversari C, Amar-Costesec A and Van Pel A: Identification of tumour rejection antigens recognized by T lymphocytes. Cancer Surv. 13:23–37. 1992.PubMed/NCBI
13	Rosenberg SA, Yang JC and Restifo NP: Cancer immunotherapy: Moving beyond current vaccines. Nat Med. 10:909–915. 2004. View Article : Google Scholar : PubMed/NCBI
14	Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, et al IMPACT Study Investigators: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 363:411–422. 2010. View Article : Google Scholar : PubMed/NCBI
15	Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, et al: gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 364:2119–2127. 2011. View Article : Google Scholar : PubMed/NCBI
16	Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, Snively J and Hersh E: Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 26:5950–5956. 2008. View Article : Google Scholar : PubMed/NCBI
17	Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP and Quinn AG: FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 62:4773–4780. 2002.PubMed/NCBI
18	Wierstra I and Alves J: FOXM1, a typical proliferation-associated transcription factor. Biol Chem. 388:1257–1274. 2007. View Article : Google Scholar : PubMed/NCBI
19	Wang IC, Chen YJ, Hughes D, Petrovic V, Major ML, Park HJ, Tan Y, Ackerson T and Costa RH: Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. Mol Cell Biol. 25:10875–10894. 2005. View Article : Google Scholar : PubMed/NCBI
20	Laoukili J, Kooistra MR, Brás A, Kauw J, Kerkhoven RM, Morrison A, Clevers H and Medema RH: FoxM1 is required for execution of the mitotic programme and chromosome stability. Nat Cell Biol. 7:126–136. 2005. View Article : Google Scholar : PubMed/NCBI
21	Kalinichenko VV, Major ML, Wang X, Petrovic V, Kuechle J, Yoder HM, Dennewitz MB, Shin B, Datta A, Raychaudhuri P, et al: Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. Genes Dev. 18:830–850. 2004. View Article : Google Scholar : PubMed/NCBI
22	Wonsey DR and Follettie MT: Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe. Cancer Res. 65:5181–5189. 2005. View Article : Google Scholar : PubMed/NCBI
23	Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, Lyubimov A and Costa RH: Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 66:1712–1720. 2006. View Article : Google Scholar : PubMed/NCBI
24	Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, Aldape KD, Xie TX, Pelloski CE, Xie K, et al: FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 66:3593–3602. 2006. View Article : Google Scholar : PubMed/NCBI
25	Chan DW, Yu SY, Chiu PM, Yao KM, Liu VW, Cheung AN and Ngan HY: Overexpression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis. J Pathol. 215:245–252. 2008. View Article : Google Scholar : PubMed/NCBI
26	Uddin S, Ahmed M, Hussain A, Abubaker J, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F, Jehan Z, et al: Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy. Am J Pathol. 178:537–547. 2011. View Article : Google Scholar : PubMed/NCBI
27	Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, et al: The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 66:2153–2161. 2006. View Article : Google Scholar : PubMed/NCBI
28	Okada K, Fujiwara Y, Takahashi T, Nakamura Y, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Mori M, et al: Overexpression of forkhead box M1 transcription factor (FOXM1) is a potential prognostic marker and enhances chemo-resistance for docetaxel in gastric cancer. Ann Surg Oncol. 20:1035–1043. 2013. View Article : Google Scholar
29	Higashihara Y, Kato J, Nagahara A, Izumi K, Konishi M, Kodani T, Serizawa N, Osada T and Watanabe S: Phase I clinical trial of peptide vaccination with URLC10 and VEGFR1 epitope peptides in patients with advanced gastric cancer. Int J Oncol. 44:662–668. 2014.PubMed/NCBI
30	Murahashi M, Hijikata Y, Yamada K, Tanaka Y, Kishimoto J, Inoue H, Marumoto T, Takahashi A, Okazaki T and Takeda K: Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors. Clin Immunol. 166–167. 48–58. 2016.
31	Suzuki N, Hazama S, Ueno T, Matsui H, Shindo Y, Iida M, Yoshimura K, Yoshino S, Takeda K and Oka M: A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer. J Immunother. 37:36–42. 2014. View Article : Google Scholar
32	Yoshimura K, Minami T, Nozawa M and Uemura H: Phase I clinical trial of human vascular endothelial growth factor receptor 1 peptide vaccines for patients with metastatic renal cell carcinoma. Br J Cancer. 108:1260–1266. 2013. View Article : Google Scholar : PubMed/NCBI
33	Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar : PubMed/NCBI
34	Iinuma H, Fukushima R, Inaba T, Tamura J, Inoue T, Ogawa E, Horikawa M, Ikeda Y, Matsutani N, Takeda K, et al: Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients. J Transl Med. 12:842014. View Article : Google Scholar : PubMed/NCBI
35	Obara W, Ohsawa R, Kanehira M, Takata R, Tsunoda T, Yoshida K, Takeda K, Katagiri T, Nakamura Y and Fujioka T: Cancer peptide vaccine therapy developed from oncoantigens identified through genome-wide expression profile analysis for bladder cancer. Jpn J Clin Oncol. 42:591–600. 2012. View Article : Google Scholar : PubMed/NCBI
36	Asahara S, Takeda K, Yamao K, Maguchi H and Yamaue H: Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. J Transl Med. 11:2912013. View Article : Google Scholar : PubMed/NCBI
37	Masuzawa T, Fujiwara Y, Okada K, Nakamura A, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Osawa R, et al: Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. Int J Oncol. 41:1297–1304. 2012.PubMed/NCBI
38	Kono K, Iinuma H, Akutsu Y, Tanaka H, Hayashi N, Uchikado Y, Noguchi T, Fujii H, Okinaka K, Fukushima R, et al: Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med. 10:1412012. View Article : Google Scholar : PubMed/NCBI
39	Finn OJ, Khleif SN and Herberman RB: The FDA guidance on therapeutic cancer vaccines: The need for revision to include preventive cancer vaccines or for a new guidance dedicated to them. Cancer Prev Res (Phila). 8:1011–1016. 2015. View Article : Google Scholar