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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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)

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Biological: protein vaccination


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: protein vaccination|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NY-ESO-1-specific immune responses |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor responses |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer/testis antigen, cancer vaccine, recombinant protein