CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma
- Haematologica. 2011 Jan;96(1):78-86. doi: 10.3324/haematol.2010.028241.
- 1. Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK.
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.