Validation of PASD1 as an immunotherapeutic target in colorectal cancer (CRC)

Abstract

Event Abstract Back to Event Validation of PASD1 as an immunotherapeutic target in colorectal cancer (CRC) Joanne E. Soh1, Nadiah Abu1, Hui-min Neoh1, Luqman Mazlan2, Azyani Yahaya3 and Rahman Jamal1* 1 UKM Medical Molecular Biology Institute (UMBI), Malaysia 2 Department of Surgery, Faculty of medicine, University of Malaya, Malaysia 3 Department of Pathology, Faculty of Medicine, National University of Malaysia, Malaysia Background Colorectal cancer (CRC) is the third commonest malignancy in Asia including Malaysia. Despite the advances in screening, surgery and conventional therapies, a significant proportion of CRC patients failed to achieve long term remission or experienced toxic side effects of treatment. The identification of PAS (Per ARNT Sim) domain containing 1 (PASD1), a promising cancer testis antigen (CTA) as an immunotherapeutic target, represents one approach to improve treatment options for CRC. The aim of the present study was to investigate the expression of PASD1 and CD8 T-cells pulsed with PASD1 immune responses in CRC patients. Methods PASD1 mRNA expression was determined via RT-PCR on paired tumors and normal tissue samples from 25 CRC patients. Tissue expression of PASD1 was assessed via immunochemistry (IHC) in another 18 CRC samples. Four immunogenic PASD1 peptides predicted to bind to Major Histocompatibility Complex (MHC) Class 1 allele were identified using web-based algorithms. Peripheral blood mononuclear cells from CRC patients were used to investigate the immunogenicity of these HLA-A*2402 restricted peptides in vitro using IFN-y release ELISpot assay. The effects of effector CD8+ T-cells pulsed with PASD1 peptides against different cancer cells were detected in cytolytic and granzyme-B release ELISpot cytotoxicity assays. Results Gene expression of PASD1 was detected in 20% (5/25) CRC samples but not its protein expression. One of the four PASD1 peptides, PASD1(4), was shown to be immunogenic in CRC patients studied via the IFN-y release ELISpot assay. CD8-positive cytotoxic T cells from three patients raised against PASD1(4) were able to lyse HLA-A*2402 positive-SW480 cell line expressing endogenous PASD1 protein in all three effector/target ratios. Conclusion This is the first report of CD8-positive CTL response to PASD1 protein in CRC patients. Preliminary results show that PASD1 peptide is a probable immunogenic antigen and represents a potential target for peptide-based immunotherapy in CRC Keywords: PASD1, colorectal cancer, HLA-A*2402, cancer immunotherapy, Cytotoxic T-cell Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Cancer Citation: Soh JE, Abu N, Neoh H, Mazlan L, Yahaya A and Jamal R (2019). Validation of PASD1 as an immunotherapeutic target in colorectal cancer (CRC). Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00047 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2018; Published Online: 17 Jan 2019. * Correspondence: Prof. Rahman Jamal, UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Malaysia, rahmanj@ppukm.ukm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Joanne E Soh Nadiah Abu Hui-min Neoh Luqman Mazlan Azyani Yahaya Rahman Jamal Google Joanne E Soh Nadiah Abu Hui-min Neoh Luqman Mazlan Azyani Yahaya Rahman Jamal Google Scholar Joanne E Soh Nadiah Abu Hui-min Neoh Luqman Mazlan Azyani Yahaya Rahman Jamal PubMed Joanne E Soh Nadiah Abu Hui-min Neoh Luqman Mazlan Azyani Yahaya Rahman Jamal Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.