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CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma
- Source :
- Haematologica. 96(1)
- Publication Year :
- 2011
-
Abstract
- BACKGROUND: Vaccine development targeting the novel immunogenic Per ARNT Sim Domain containing 1 (PASD1) cancer testis antigen represents an attractive therapeutic approach for the significant number of patients with diffuse large B-cell lymphoma who are refractory to conventional treatment. Since CD4-positive T helper cells have crucial roles in promoting and maintaining immune responses to tumor antigens, the presence of a CD4-positive T-helper immune response to the PASD1 antigen in patients with diffuse large B-cell lymphoma was investigated in the current study. DESIGN AND METHODS: Thirty-one patients with diffuse large B-cell lymphoma (25 with de novo, five with transformed and one with T-cell-rich B-cell lymphoma) were studied. Five immunogenic PASD1 peptides predicted to bind to several major histocompatibiliy complex, class II DR beta 1 alleles were identified using web-based algorithms. Peripheral blood mononuclear cells from patients were used to investigate the immunogenicity of these DR beta 1-restricted peptides in vitro using both gamma-interferon release enzyme-linked immunospot and cytolytic assays. RESULTS: Two of the five PASD1 peptides, PASD1(6) and PASD1(7), were shown to be immunogenic in 14 out of 32 patients studied in a gamma-interferon release assay. CD4-positive T-helper cell lines from two patients raised against PASD1 peptides were able to lyse cell lines derived from hematologic malignancies expressing endogenous PASD1 protein. CONCLUSIONS: This is the first report of a CD4-positive T-helper response to the PASD1 protein in patients with lymphoma. The immunogenic peptides described here represent valuable additional candidates for inclusion in a vaccine to treat patients with PASD1-positive diffuse large B-cell lymphoma whose disease is refractory to conventional therapies.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Male
Blotting, Western
Fluorescent Antibody Technique
Enzyme-Linked Immunosorbent Assay
Biology
Immunoenzyme Techniques
Immune system
Antigen
Antigens, Neoplasm
medicine
Humans
Aged
Aged, 80 and over
Immunogenicity
Antigens, Nuclear
T-Lymphocytes, Helper-Inducer
Hematology
T helper cell
Middle Aged
Prognosis
medicine.disease
Peptide Fragments
BCL10
Lymphoma
medicine.anatomical_structure
Immunology
Cancer/testis antigens
Female
Original Article
Lymphoma, Large B-Cell, Diffuse
Diffuse large B-cell lymphoma
T-Lymphocytes, Cytotoxic
Subjects
Details
- Language :
- English
- ISSN :
- 15928721 and 03906078
- Volume :
- 96
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....ea6fff20f964d53acc4af76f26178e64