Safety Study of NY-ESO-1 Protein Vaccine to Treat Cancer Expressing NY-ESO-1 - Full Text View

Purpose

The purpose of this study is to assess the safety of repeated doses of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and describe the NY-ESO-1 specific-humoral and cellular immune response to immunization with CHP-NY-ESO-1 in patients with cancer expressing NY-ESO-1.

Condition	Intervention	Phase
Neoplasms	Biological: protein vaccination	Phase I

MedlinePlus related topics:

Cancer Cholesterol

ChemIDplus related topics:

Cholest-5-en-3-ol (3beta)-

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Official Title:	Immunization of Patients With Tumors Expressing NY-ESO-1 or LAGE Antigen With Complex of NY-ESO-1 Protein and Cholesterol-Bearing Hydrophobized Pullulan (CHP)

Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:

NY-ESO-1-specific immune responses

Secondary Outcome Measures:

tumor responses

Estimated Enrollment:	9
Study Start Date:	June 2004
Study Completion Date:	December 2006

Detailed Description:

NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of CT antigens. NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. LAGE-1 was identified by the representational difference analysis and revealed to display 84% amino acid homology with NY-ESO-1. In most cases, expression of LAGE-1 parallels the expression of NY-ESO-1. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific.

Because of frequent NY-ESO-1 mRNA expression and high immunogenicity in advanced cancer, NY-ESO-1 is an attractive target molecule for a cancer vaccine. Current therapies against advanced cancer have limited effectiveness. The idea of vaccination with NY-ESO-1 protein in cancer patients with tumors expressing NY-ESO-1 mRNA is based on two findings: 1) the number of CD8+ T cell epitopes identified in NY-ESO-1 molecule are limited to those binding to HLA-A0201, A31, Cw3 and Cw6. These HLA subtypes are carried by a minor Japanese population; 2) CD8+ T cell responses specific to NY-ESO-1 are polyclonal. Protein vaccination may induce immune response more effectively against tumors expressing NY-ESO-1 than peptide immunization.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically proven cancer
Confirmed NY-ESO-1 expression
No other effective therapy available
4 weeks since conventional therapy before start of the current protocol
Performance status < 2 (ECOG scale)
Age > 18
Able and willing to give written informed consent

Exclusion Criteria:

Serious illness
Metastatic diseases to central nervous system
Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or NSAIDs
HIV positive
Mental impairment that may compromise the ability to give written informed consent
Pregnancy and breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00106158

Locations


Japan
	Dept. of Immunology, Okayama University School of Medicine and Dentistry
	Okayama, Japan, 700-8558

Sponsors and Collaborators

Ludwig Institute for Cancer Research

Investigators


Principal Investigator:	Eiichi Nakayama, MD., PhD	Dept. of Immunology, Okayama University Schhol of Medicine and Dentistry

More Information

In Japanese This link exits the ClinicalTrials.gov site

Publications:

Sato S, Noguchi Y, Wada H, Fujita S, Nakamura S, Tanaka R, Nakada T, Hasegawa K, Nakagawa K, Koizumi F, Ono T, Nouso K, Jungbluth A, Chen YT, Old LJ, Shiratori Y, Nakayama E. Quantitative real-time RT-PCR analysis of NY-ESO-1 and LAGE-1a mRNA expression in normal tissues and tumors, and correlation of the protein expression with the mRNA copy number. Int J Oncol. 2005 Jan;26(1):57-63.

Sugita Y, Wada H, Fujita S, Nakata T, Sato S, Noguchi Y, Jungbluth AA, Yamaguchi M, Chen YT, Stockert E, Gnjatic S, Williamson B, Scanlan MJ, Ono T, Sakita I, Yasui M, Miyoshi Y, Tamaki Y, Matsuura N, Noguchi S, Old LJ, Nakayama E, Monden M. NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors. Cancer Res. 2004 Mar 15;64(6):2199-204.

Nakada T, Noguchi Y, Satoh S, Ono T, Saika T, Kurashige T, Gnjatic S, Ritter G, Chen YT, Stockert E, Nasu Y, Tsushima T, Kumon H, Old LJ, Nakayama E. NY-ESO-1 mRNA expression and immunogenicity in advanced prostate cancer. Cancer Immun. 2003 Jul 31;3:10.

Fujita S, Wada H, Jungbluth AA, Sato S, Nakata T, Noguchi Y, Doki Y, Yasui M, Sugita Y, Yasuda T, Yano M, Ono T, Chen YT, Higashiyama M, Gnjatic S, Old LJ, Nakayama E, Monden M. NY-ESO-1 expression and immunogenicity in esophageal cancer. Clin Cancer Res. 2004 Oct 1;10(19):6551-8.

Kurashige T, Noguchi Y, Saika T, Ono T, Nagata Y, Jungbluth A, Ritter G, Chen YT, Stockert E, Tsushima T, Kumon H, Old LJ, Nakayama E. Ny-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tumor grade. Cancer Res. 2001 Jun 15;61(12):4671-4.

Study ID Numbers:	LUD2002-005
First Received:	March 21, 2005
Last Updated:	August 21, 2007
ClinicalTrials.gov Identifier:	NCT00106158
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Ludwig Institute for Cancer Research:

cancer/testis antigen

cancer vaccine

recombinant protein

Study placed in the following topic categories:

Testicular Diseases

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on September 23, 2008

Sponsored by:	Ludwig Institute for Cancer Research
Information provided by:	Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:	NCT00106158