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

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.

Author dc:creator

• Neilson, David S

Advisor dc:contributor.supervisor

• Lum, Julian J

• Immunotherapy
• Ovarian Cancer
• CD8 T cell
• Antigen Discovery
• Lactate Dehydrogenase C

Statement dc:rights

• Available to the World Wide Web

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/2.5/ca/

Language dc:language.iso

en, English

Handle dc:identifier.uri

http://hdl.handle.net/1828/7692

OAI identifier oai:identifier

oai:dspace.library.uvic.ca:1828/7692