Format

Send to

Choose Destination
Oncotarget. 2015 Sep 22;6(28):25356-67. doi: 10.18632/oncotarget.4516.

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

Author information

1
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
2
BioNTech Cell & Gene Therapies, An der Goldgrube 12, Mainz, Germany.
3
Experimental Oncology, Department of Medicine III, Johannes Gutenberg-University, Mainz, Germany.

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.

KEYWORDS:

CD8+ T cell epitope; CXorf61; T-cell receptor cloning; TNBC; immunotherapy

PMID:
26327325
PMCID:
PMC4694836
DOI:
10.18632/oncotarget.4516
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center