CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer.
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.
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Claudia
C
Paret
BioNTech Cell & Gene Therapies, An der Goldgrube 12, Mainz, Germany.
Petra
P
Simon
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Kirsten
K
Vormbrock
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Christian
C
Bender
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Anne
A
Kölsch
BioNTech Cell & Gene Therapies, An der Goldgrube 12, Mainz, Germany.
Andrea
A
Breitkreuz
BioNTech Cell & Gene Therapies, An der Goldgrube 12, Mainz, Germany.
Özlem
Ö
Yildiz
BioNTech Cell & Gene Therapies, An der Goldgrube 12, Mainz, Germany.
Tana
T
Omokoko
Experimental Oncology, Department of Medicine III, Johannes Gutenberg-University, Mainz, Germany.
Stefanie
S
Hubich-Rau
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.|Experimental Oncology, Department of Medicine III, Johannes Gutenberg-University, Mainz, Germany.
Christoph
C
Hartmann
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Sabine
S
Häcker
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.|Experimental Oncology, Department of Medicine III, Johannes Gutenberg-University, Mainz, Germany.
Meike
M
Wagner
Experimental Oncology, Department of Medicine III, Johannes Gutenberg-University, Mainz, Germany.
Diana Barea
DB
Roldan
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Abderaouf
A
Selmi
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Özlem
Ö
Türeci
TRON gGmbH, Translational Oncology at the University Medical Center, Johannes Gutenberg-University, Mainz, Germany.|BioNTech Cell & Gene Therapies, An der Goldgrube 12, Mainz, Germany.|Experimental Oncology, Department of Medicine III, Johannes Gutenberg-University, Mainz, Germany.
Ugur
U
Sahin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D018920:Coculture Techniques; D019175:DNA Methylation; D018604:Epitope Mapping; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007115:Immunization Schedule; D020014:K562 Cells; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008822:Mice, Transgenic; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000951:Antigens, Neoplasm; C000600054:CT83 protein, human; D019496:Cancer Vaccines; C524866:HLA-A*02 antigen; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic
CD8+ T cell epitope; CXorf61; T-cell receptor cloning; TNBC; immunotherapy