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Published in: Gastric Cancer 1/2014

01-01-2014 | Original Article

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

Published in: Gastric Cancer | Issue 1/2014

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Abstract

Background

Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer.

Methods

LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund’s adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course.

Results

LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient.

Conclusions

LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
2.
go back to reference Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer. 1993;54:594–606.PubMedCrossRef Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer. 1993;54:594–606.PubMedCrossRef
3.
go back to reference Maruyama K, Kaminishi M, Hayashi K, Isobe Y, Honda I, Katai H, et al. Gastric cancer treated in 1991 in Japan: data analysis of nationwide registry. Japanese Gastric Cancer Association Registration Committee. Gastric Cancer. 2006;9:51–66.PubMedCrossRef Maruyama K, Kaminishi M, Hayashi K, Isobe Y, Honda I, Katai H, et al. Gastric cancer treated in 1991 in Japan: data analysis of nationwide registry. Japanese Gastric Cancer Association Registration Committee. Gastric Cancer. 2006;9:51–66.PubMedCrossRef
4.
go back to reference Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000;58:191–7.PubMedCrossRef Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000;58:191–7.PubMedCrossRef
5.
go back to reference Takiuchi H, Narahara H, Tsujinaka T, Gotoh M, Kawabe S, Katsu K, et al. Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced gastric cancer (OGSG 0002). Jpn J Clin Oncol. 2005;35:520–525. Takiuchi H, Narahara H, Tsujinaka T, Gotoh M, Kawabe S, Katsu K, et al. Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced gastric cancer (OGSG 0002). Jpn J Clin Oncol. 2005;35:520–525.
6.
go back to reference Yoshida K, Ninomiya M, Takakura N, Hirabayashi N, Takiyama W, Sato Y, et al. Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Clin Cancer Res. 2006;12:3402–7.PubMedCrossRef Yoshida K, Ninomiya M, Takakura N, Hirabayashi N, Takiyama W, Sato Y, et al. Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Clin Cancer Res. 2006;12:3402–7.PubMedCrossRef
7.
go back to reference Kikuchi T, Daigo Y, Katagiri T, Tsunoda T, Okada K, Kakiuchi S, et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene. 2003;22:2192–205.PubMedCrossRef Kikuchi T, Daigo Y, Katagiri T, Tsunoda T, Okada K, Kakiuchi S, et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene. 2003;22:2192–205.PubMedCrossRef
8.
go back to reference Kakiuchi S, Daigo Y, Ishikawa N, Furukawa C, Tsunoda T, Yano S, et al. Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004;13:3029.PubMedCrossRef Kakiuchi S, Daigo Y, Ishikawa N, Furukawa C, Tsunoda T, Yano S, et al. Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004;13:3029.PubMedCrossRef
9.
go back to reference Kikuchi T, Daigo Y, Ishikawa N, Katagiri T, Tsunoda T, Yoshida S, et al. Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray. Int J Oncol. 2006;28:799.PubMed Kikuchi T, Daigo Y, Ishikawa N, Katagiri T, Tsunoda T, Yoshida S, et al. Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray. Int J Oncol. 2006;28:799.PubMed
10.
go back to reference Taniwaki M, Daigo Y, Ishikawa N, Takano A, Tsunoda T, Yasui W, et al. Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer. Int J Oncol. 2006;29:567–75.PubMed Taniwaki M, Daigo Y, Ishikawa N, Takano A, Tsunoda T, Yasui W, et al. Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer. Int J Oncol. 2006;29:567–75.PubMed
11.
go back to reference Yamabuki T, Daigo Y, Kato T, Hayama S, Tsunoda T, Miyamoto M, et al. Genome-wide gene expression profile analysis of esophageal squamous-cell carcinomas. Int J Oncol. 2006;28:1375–84.PubMed Yamabuki T, Daigo Y, Kato T, Hayama S, Tsunoda T, Miyamoto M, et al. Genome-wide gene expression profile analysis of esophageal squamous-cell carcinomas. Int J Oncol. 2006;28:1375–84.PubMed
12.
go back to reference Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, et al. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007;67:11601–11.PubMedCrossRef Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, et al. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007;67:11601–11.PubMedCrossRef
13.
go back to reference Kono K, Mizukami Y, Daigo Y, Takano A, Masuda K, Yoshida K, et al. Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer. Cancer Sci. 2009;100:1502–9.PubMedCrossRef Kono K, Mizukami Y, Daigo Y, Takano A, Masuda K, Yoshida K, et al. Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer. Cancer Sci. 2009;100:1502–9.PubMedCrossRef
14.
go back to reference Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, et al. Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma. Cancer Sci. 2010;101:2510–7. doi:10.1111/j.1349-7006.2010.01732.x.PubMedCrossRef Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, et al. Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma. Cancer Sci. 2010;101:2510–7. doi:10.​1111/​j.​1349-7006.​2010.​01732.​x.PubMedCrossRef
15.
go back to reference de Nooij-van Dalen AG, van Dongen GA, Smeets SJ, Nieuwenhuis EJ, Stigter-van Walsum M, Snow GB, et al. Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma. Int J Cancer. 2003;103:768–74.PubMedCrossRef de Nooij-van Dalen AG, van Dongen GA, Smeets SJ, Nieuwenhuis EJ, Stigter-van Walsum M, Snow GB, et al. Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma. Int J Cancer. 2003;103:768–74.PubMedCrossRef
16.
go back to reference Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.PubMed Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.PubMed
17.
go back to reference Lee JW, Lee YS, Yoo KH, Lee KH, Park K, Ahn T, et al. LY-6K gene: a novel molecular marker for human breast cancer. Oncol Rep. 2006;16:1211–4.PubMed Lee JW, Lee YS, Yoo KH, Lee KH, Park K, Ahn T, et al. LY-6K gene: a novel molecular marker for human breast cancer. Oncol Rep. 2006;16:1211–4.PubMed
18.
go back to reference Choi SH, Kong HK, Park SY, Park JH. Metastatic effect of LY-6K gene in breast cancer cells. Int J Oncol. 2009;35:601–7.PubMed Choi SH, Kong HK, Park SY, Park JH. Metastatic effect of LY-6K gene in breast cancer cells. Int J Oncol. 2009;35:601–7.PubMed
19.
go back to reference Matsuda R, Enokida H, Chiyomaru T, Kikkawa N, Sugimoto T, Kawakami K, et al. LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling. Br J Cancer. 2011;104:376–86.PubMedCentralPubMedCrossRef Matsuda R, Enokida H, Chiyomaru T, Kikkawa N, Sugimoto T, Kawakami K, et al. LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling. Br J Cancer. 2011;104:376–86.PubMedCentralPubMedCrossRef
20.
go back to reference Kawakami Y, Fujita T, Matsuzaki Y, Sakurai T, Tsukamoto M, Toda M, et al. Identification of human tumor antigens and its implications for diagnosis and treatment of cancer. Cancer Sci. 2004;95:10. Kawakami Y, Fujita T, Matsuzaki Y, Sakurai T, Tsukamoto M, Toda M, et al. Identification of human tumor antigens and its implications for diagnosis and treatment of cancer. Cancer Sci. 2004;95:10.
21.
go back to reference Yataro D, Yusuke N. From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Gen Thorac Cardiovasc Surg. 2008;56:43–53.CrossRef Yataro D, Yusuke N. From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Gen Thorac Cardiovasc Surg. 2008;56:43–53.CrossRef
22.
go back to reference Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, et al. Phase I trial of a melanoma vaccine with gp100280–288 peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes. Clin Cancer Res. 2001;7:3012–24.PubMed Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, et al. Phase I trial of a melanoma vaccine with gp100280–288 peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes. Clin Cancer Res. 2001;7:3012–24.PubMed
23.
Metadata
Title
Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer
Publication date
01-01-2014
Published in
Gastric Cancer / Issue 1/2014
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-013-0258-6

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