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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.

The identification of immunogenic cancer testis antigens (CTAs) as immunotherapeutic targets represents one approach to improve treatment options for diffuse large B-cell lymphoma (DLBCL). We previously identified PASD1 [PAS (Per ARNT Sim) domain containing 1 (PASD1)], a DLBCL-associated CTA that was expressed in a range of hematopoietic malignancies. The aim of the present study was to investigate the presence of a cytotoxic T-cell (CTL) response to PASD1 in DLBCL patients. A significant gamma-interferon (IFN) release was detected in 21/29 HLA-A*0201-positive DLBCL patients (18 de novo DLBCL, two transformed DLBCL and one T-cell rich B-cell lymphoma) following short-term culture of their peripheral blood mononuclear cells stimulated with five HLA-A*0201-restricted PASD1 peptides. No significant responses were detected in 21 HLA-A*0201-negative DLBCL patients (12 de novo DLBCL, seven transformed DLBCL, two T-cell rich B-cell lymphoma) or six normal subjects. CTL cell lines were able to lyse PASD1-positive tumour cells in a major histocompatibility complex-Class I dependent manner. The presence of a gamma-IFN response correlated with PASD1 protein expression in the tumour cells in 12/15 cases studied. This is the first report of a CTL response to a CTA in DLBCL. Our results provide additional valuable evidence supporting PASD1 as a potential immunotherapeutic target for the treatment of DLBCL and other malignancies.

Early in the year 1923, the Directors of the Consolidated Water Works Company of Rosario de Santa Fe, Argentine Republic, in view of the trouble experienced from corrosion and tuberculation of their distribution system, decided that all extensions and renewals should in the future be laid with cement-lined pipe, the lining to be applied centrifugally with the object of assuring both its impermeability and its rigid adhesion to the metal. Because of the limited number of manufacturers then in a position to supply centrifugally cement-lined pipe, full advantage could not be taken of trade competition to purchase pipes under the most favourable conditions. Furthermore, the extra freight charges on the weight of the lining combined to raise the price of these pipes considerably above that of the unlined variety. It became evident, therefore, that, if a convenient process could be devised, whereby lining operations could be carried out on the spot by the Company, the extra freight charges mentioned would be eliminated and purchases of the unlined pipes could be made in the open market. Essential features of any such process had of necessity to be: (1) low capital cost of the installation; (2) adaptability to a wide range of pipe diameters, and (3) economical results. The process ultimately decided upon, and developed, consists of applying to a pipe, into which has previously been introduced a measured quantity of semi-liquid cement mortar, a rotary motion by rolling down a suitable incline under the action of gravity, and of utilising the centrifugal force thus generated to project and consolidate around the interior of the pipe wall a uniform layer of the cement mortar referred to. In actual practice at Rosario, two sets of parallel rails are laid on