PASD1: A Promising Target for the Immunotherapy of Haematological Malignancies

Khan, Ghazala; Denniss, Frances; Mills, Ken I; Guinn, Barbara-ann; Pulford, Karen

Abstract

In general, there is a lack of good immunotherapy targets within the spectrum of haematological malignancies. However haematopoietic stem cell transplants and continuing antigen discovery have allowed further insight into how further improvements in outcomes for patients might be achieved. Most patients with haematological malignancies can be treated with conventional therapies such as radio- and chemotherapy and will attain first remission. However the removal of residual diseased cells is essential to prevent relapse and its associated high mortality. PASD1 is one of the most tissue restricted cancer-testis (CT) antigens with expression limited to primary spermatagonia in healthy tissue. However, characterisation of PASD1 expression in cancers has been predominantly focussed on haematological malignancies where the inappropriate expression of PASD1 was first identified. PASD1 has one of the highest frequencies of expression of all CT antigens in acute myeloid leukaemia, with some suggestion of its role as a biomarker in diffuse large B-cell lymphoma. Here we describe the characterisation of the function and expression patterns of PASD1 in cell lines and primary tissues. Development of DNA vaccines targeting PASD1 epitopes demonstrate effective ex vivo T-cell responses in terms of IFNγ secretion and tumour cell killing. Of particular note these vaccines have led to the destruction of cells which process and present endogenous PASD1 indicating that effectively primed CTLs could kill PASD1-positive tumour cells.

Citation

Khan, G., Denniss, F., Mills, K. I., Guinn, B.-A., & Pulford, K. (2013). PASD1: A Promising Target for the Immunotherapy of Haematological Malignancies. Genetic Syndromes and Gene Therapy, 04(09), Article 186. https://doi.org/10.4172/2157-7412.1000186

• Journal Article Type: Article
• Acceptance Date: Sep 30, 2013
• Online Publication Date: Oct 10, 2013
• Publication Date: Oct 10, 2013
• Deposit Date: Apr 9, 2019
• Publicly Available Date: Apr 11, 2019
• Journal: Journal of Genetic Syndromes & Gene Therapy
• Print ISSN: 2157-7412
• Publisher: OMICS International
• Peer Reviewed: Peer Reviewed
• Volume: 04
• Issue: 09
• Article Number: 186
• DOI: https://doi.org/10.4172/2157-7412.1000186
• Keywords: PASD1; Immunotherapy; Cancer; Tumour antigen; Cancer-testis antigen
• Public URL: https://hull-repository.worktribe.com/output/1567222
• Publisher URL: https://www.omicsonline.org/pasd-a-promising-target-for-the-immunotherapy-of-haematological-malignancies-2157-7412.1000186.php?aid=19315
• Contract Date: Apr 11, 2019