PASD1, a DLBCL-associated cancer testis antigen and candidate for lymphoma immunotherapy

Cooper, C.D.O.; Liggins, Amanda P.; Ait-Tahar, Kamel; Roncador, Giovanna; Banham, Alison H.; Pulford, Karen

doi:10.1038/sj.leu.2404424

Cited by 28 publications

(51 citation statements)

References 7 publications

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“…Protein expression was tracked immunohistochemically, using a novel monoclonal antibody 2ALCC128, recognizing a unique C-terminal epitope in PASD1_v2. 4 The MM cell lines THIEL and RPMI8226 expressed both mRNA and protein for PASD1, whereas JJN3 lacked both ( Figure 1A,C). Protein expression was also confirmed in 2 of 4 primary MM tumor samples examined ( Figure 1C).…”

Section: Pasd1 Is a Potential Multiple Myeloma-associated Antigenmentioning

confidence: 99%

PASD1 is a potential multiple myeloma–associated antigen

Sahota¹,

Goonewardena²,

Cooper³

et al. 2006

Blood

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Section: Pasd1 Is a Potential Multiple Myeloma-associated Antigenmentioning

confidence: 99%

PASD1 is a potential multiple myeloma–associated antigen

Sahota¹,

Goonewardena²,

Cooper³

et al. 2006

Blood

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“…18 We initially identified PASD1 as a tumor-associated antigen in DLBCL 19 and acute myeloid leukemia 20 while later studies showed PASD1 to be a novel cancer-testis antigen expressed in a wide range of hematologic malignancies. 21,22 Our subsequent identification of a CTL response to PASD1 in DLBCL 23 supports this molecule as a candidate for vaccine development, not only for DLBCL, but also for use in a generic vaccine for the treatment of other PASD1-positive malignancies. The current study was performed to investigate the CD4 Th response in DLBCL patients to obtain further support for the inclusion of PASD1 in a lymphoma vaccine.…”

Section: Introductionmentioning

confidence: 67%

“…35 Importantly, high levels of target protein expression may not be necessary for immune recognition. 36 There is also evidence that additional isoforms of PASD1 may exist 21 and some of these proteins may lack the epitopes recognized by the PASD1-1 and PASD1-2 antibodies that are currently being used to study PASD1 protein expression. The development of more sensitive assays for PASD1 expression, such as western blotting and/or the production of additional antibodies, should assist in the identification of the maximum number of PASD1-positive patients in future clinical trials targeting K. AIt-Taha et al 84 haematologica | 2011; 96(1) Figure 3.…”

Section: Discussionmentioning

confidence: 99%

CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma

Ait-Tahar¹,

Liggins²,

Collins³

et al. 2010

Haematologica

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BackgroundVaccine 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 MethodsThirty-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. ResultsTwo 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. ConclusionsThis 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. -cell lymphoma. Haematologica 2011;96(1):78-86. doi:10.3324/haematol.2010 This is an open-access paper. CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma

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“…There are a number of assays which can be used to validate the expression of antigens in tumour cells. Many of the most frequently used rely on an available antibody which has been validated [50,51]. Techniques frequently used include:-…”

Section: Validation Of the Expression Of Tumour Antigens In Tumour Cellsmentioning

confidence: 99%

Identification and Validation of Targets for Cancer Immunotherapy: From the Bench-to-Bedside

Khan¹,

Brooks²,

Denniss³

et al. 2013

Novel Gene Therapy Approaches

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PASD1, a DLBCL-associated cancer testis antigen and candidate for lymphoma immunotherapy

Cited by 28 publications

References 7 publications

PASD1 is a potential multiple myeloma–associated antigen

PASD1 is a potential multiple myeloma–associated antigen

CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma

Identification and Validation of Targets for Cancer Immunotherapy: From the Bench-to-Bedside

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