Investigation of the cancer testis antigen lactate dehydrogenase C as a CD8 T cell target

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dc.contributor.authorNeilson, David S
dc.contributor.supervisorLum, Julian J
dc.date.accessioned2016-12-23T17:55:21Z
dc.date.available2016-12-23T17:55:21Z
dc.date.copyright2016en_US
dc.date.issued2016-12-23
dc.degree.departmentDepartment of Biochemistry and Microbiologyen_US
dc.degree.levelMaster of Science M.Sc.en_US
dc.description.abstractThe infrequency of known T cell targets in high grade serous ovarian carcinoma (HSGC) is a substantial barrier to the development of targeted immunotherapies. Due to their infrequency, antigen discovery is a crucial component of immunotherapeutic design. In our cohort of HGSC cases, the cancer testis (CT) antigen lactate dehydrogenase C (LDHC) is expressed in 76% of tumours (22/29). As LDHC presents with tumour specificity in women, I hypothesize that LDHC is an immunogenic target in HGSC patients, and that LDHC-specific T cells can be activated and expanded for therapeutic purposes. As such, I sought to examine whether endogenous LDHC-specific T cells were present in the ascites of HGSC patients. A standard Rapid Expansion Protocol was used to expand CD8 T cell cultures from patient ascites. These cultures were screened for reactivity to a peptide library encompassing all possible epitopes of the LDHC protein by interferon-γ ELISpot. With this approach, T cell clones from one of five patients were identified that were reactive to minimal peptides contained within LDHC. In this patient, the antigenic LDHC peptide differentiated from LDHA by a single amino acid at its C-terminus (YTSWAIGLSVM versus YTSWAIGLSVA). In recognition assays, tumour cell lines expressing endogenous LDHC, autologous ascites, or autologous B cells transfected with LDHC were unable to elicit T cell responses. Although this study suggests that LDHC is not immunogenic, continued screening of LDHC and other CT proteins will likely provide additional immunotherapeutic targets.en_US
dc.description.scholarlevelGraduateen_US
dc.identifier.urihttp://hdl.handle.net/1828/7692
dc.languageEnglisheng
dc.language.isoenen_US
dc.rightsAvailable to the World Wide Weben_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/ca/*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/ca/*
dc.subjectImmunotherapyen_US
dc.subjectOvarian Canceren_US
dc.subjectCD8 T cellen_US
dc.subjectAntigen Discoveryen_US
dc.subjectLactate Dehydrogenase Cen_US
dc.titleInvestigation of the cancer testis antigen lactate dehydrogenase C as a CD8 T cell targeten_US
dc.typeThesisen_US

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