{"id":{"repo_id":"uvic","oai_identifier":"oai:dspace.library.uvic.ca:1828/7692"},"canonical_url":"https://search.dev.ndltd.org/etd/uvic/oai:dspace.library.uvic.ca:1828/7692","repository":{"repo_id":"uvic","name":"University of Victoria (Canada)","base_url":"https://dspace.library.uvic.ca/server/oai/request"},"display":{"title":"Investigation of the cancer testis antigen lactate dehydrogenase C as a CD8 T cell target","abstract":"The 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.","abstract_html":"The 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.","abstract_has_math":false,"creators":["Neilson, David S"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Lum, Julian J"],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-12-23","date_published":"2016-12-23","updated_at":"2026-07-24T05:52:40Z","subjects":["Immunotherapy","Ovarian Cancer","CD8 T cell","Antigen Discovery","Lactate Dehydrogenase C"],"languages":["en","English"],"rights":["Available to the World Wide Web"],"rights_urls":["http://creativecommons.org/licenses/by-nc-nd/2.5/ca/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1828/7692","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.supervisor","label":"Supervisor","values":["Lum, Julian J"]},{"key":"dc:creator","label":"Author","values":["Neilson, David S"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-12-23T17:55:21Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-12-23T17:55:21Z"]},{"key":"dc:date.issued","label":"Date","values":["2016-12-23"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunotherapy","Ovarian Cancer","CD8 T cell","Antigen Discovery","Lactate Dehydrogenase C"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Available to the World Wide Web"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-nd/2.5/ca/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1828/7692"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The 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."]},{"key":"dc:title","label":"Title","values":["Investigation of the cancer testis antigen lactate dehydrogenase C as a CD8 T cell target"]}]}],"canonical_facts":{"dc:contributor.supervisor":["Lum, Julian J"],"dc:creator":["Neilson, David S"],"dc:date.accessioned":["2016-12-23T17:55:21Z"],"dc:date.available":["2016-12-23T17:55:21Z"],"dc:date.issued":["2016-12-23"],"dc:description.abstract":["The 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."],"dc:identifier.uri":["http://hdl.handle.net/1828/7692"],"dc:language":["English"],"dc:language.iso":["en"],"dc:rights":["Available to the World Wide Web"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-nd/2.5/ca/"],"dc:subject":["Immunotherapy","Ovarian Cancer","CD8 T cell","Antigen Discovery","Lactate Dehydrogenase C"],"dc:title":["Investigation of the cancer testis antigen lactate dehydrogenase C as a CD8 T cell target"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T05:52:40Z"}