A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil; OK-432 and Montanide; ISA-51 in patients with cancers expressing NY-ESO-1 antige
- Conditions
- advanced esophageal cancer, stomach cancer, non-small cell lung cancer (NSCLC), malignant melanoma
- Registration Number
- JPRN-UMIN000001260
- Lead Sponsor
- Department of Immunology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
- Brief Summary
We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 mcg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete: follow-up complete
- Sex
- All
- Target Recruitment
- 30
Not provided
1.Clinically significant heart disease (i.e., NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias). 2.Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders. 3.Previous bone marrow or stem cell transplant. 4.History of immunodeficiency disease or autoimmune disease except vitiligo. 5.Metastatic disease to the central nervous system, unless treated and stable. 6.Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ. 7.Known HIV, positivity. 8.Concomitant treatment with steroids. Topical or inhalational steroids are permitted. (See also Section 6.7 for restrictions/recommendations on 'Ancillary Therapy'.) 9.Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent. 10.Pregnancy or lactation. 11.Women of childbearing potential not using a medically acceptable means of contraception. 12.Psychiatric or addictive disorders that may compromise the ability to give informed consent. 13.Lack of availability of the patient for immunological and clinical follow-up assessment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Toxicities and adverse events defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Scale.
- Secondary Outcome Measures
Name Time Method Y-ESO-1 specific immunitywill be assessed using blood obtained at baseline, every visit for vaccination and 4 weeks after the sixth vaccination. NY-ESO-1 reactive antibodies measured by ELISA and cellular immunity by NY-ESO-1 specific CD4 and CD8 T cells by cytokine secretion as determined by FACS analysis will be assayed. Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Disease status will be assessed at baseline, week 13, and 4-6 weeks after the sixth vaccination in patients with evaluable (measurable and non-measurable) disease.