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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.

Original publication

DOI

10.3324/haematol.2010.028241

Type

Journal article

Journal

Haematologica

Publication Date

01/2011

Volume

96

Pages

78 - 86

Keywords

Adult, Aged, Aged, 80 and over, Antigens, Neoplasm, Antigens, Nuclear, Blotting, Western, CD4-Positive T-Lymphocytes, Enzyme-Linked Immunosorbent Assay, Female, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Peptide Fragments, Prognosis, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer