CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is a high medical need disease with limited treatment options. CD8+ T cell-mediated immunotherapy may represent an attractive approach to address TNBC. The objectives of this study were to assess the expression of CXorf61 in TNBCs and healthy tissues and to evaluate its capability to induce T cell responses.We show by transcriptional profiling of a broad comprehensive set of normal human tissue that CXorf61 expression is strictly restricted to testis. 53% of TNBC patients express this antigen in at least 30% of their tumor cells. In CXorf61-negative breast cancer cell lines CXorf61 expression is activated by treatment with the hypomethylating agent 5-aza-2′-deoxycytidine.By vaccination of HLA-A*02-transgenic mice with CXorf61 encoding RNA we obtained high frequencies of CXorf61-specific T cells. Cloning and characterization of T cell receptors (TCRs) from responding T cells resulted in the identification of the two HLA-A*0201-restricted T cell epitopes CXorf6166–74 and CXorf6179–87. Furthermore, by in vitro priming of human CD8+ T cells derived from a healthy donor recognizing CXorf6166–74 we were able to induce a strong antigen-specific immune response and clone a human TCR recognizing this epitope.In summary, our data confirms this antigen as promising target for T cell based therapies.

Hypomethylation‐mediated activation of cancer/testis antigen KK‐LC‐1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling

“…2,3 Kita-Kyushu lung cancer antigen-1 (KK-LC-1), encoded by CT83 or Cxorf61 gene, has been characterized as a CT antigen. 6 The expression rate of KK-LC-1 in human malignancies is markedly higher than the rates of other CT antigens. 6 The expression rate of KK-LC-1 in human malignancies is markedly higher than the rates of other CT antigens.…”

“…6 The expression rate of KK-LC-1 in human malignancies is markedly higher than the rates of other CT antigens. 9 KK-LC-1 is cancer cell selective and immunogenic, and expressed at high level and frequency in cancers, 6 making it an ideal cancer immunotherapy target. 9 KK-LC-1 is cancer cell selective and immunogenic, and expressed at high level and frequency in cancers, 6 making it an ideal cancer immunotherapy target.…”

Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer

“…KK-LC-1 is a shared tumor antigen expressed in 40% (12/30) of metastatic cervical cancers tested using real-time qPCR (data not shown). Additionally, this antigen is reported to be expressed in gastric (81%) (24), triple-negative breast (53%) (25) and non-small cell lung (40%) (26) cancers. Importantly, KK-LC-1 is not expressed in normal tissues, except for the testis (25), suggesting it may be safely targeted by T cells.…”

“…Additionally, this antigen is reported to be expressed in gastric (81%) (24), triple-negative breast (53%) (25) and non-small cell lung (40%) (26) cancers. Importantly, KK-LC-1 is not expressed in normal tissues, except for the testis (25), suggesting it may be safely targeted by T cells. Indeed, patient 3853 received ~50 billion KK-LC-1-specific CD8 + T cells which persisted long-term at levels >2.5% without causing discernable autoimmune toxicities.…”

Helicobacter Pylori Infection Induces Gastric Cancer and the Cancer/Testis Antigens Expression

“…Hence, KK-LC-1 seems a potential candidate for the diagnosis of early gastric cancer. In addition, KK-LC-1 is frequently expressed in 75% of patients with triple-negative breast cancer [21]. KK-LC-1 therapy would be an attractive option for patients with TNBC because no existing hormone or antibody therapy is employed.…”