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PLoS One. 2017 Jun 8;12(6):e0179201. doi: 10.1371/journal.pone.0179201. eCollection 2017.

Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses.

Author information

1
University of Gdansk, Department of Chemistry, Gdansk, Poland.
2
SIB Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Genopode, Lausanne, Switzerland.
3
Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
4
Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France.
5
Ludwig Center for Cancer Research of the University of Lausanne, Epalinges, Switzerland.
6
Department of Oncology, University of Lausanne and University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
7
Department of Oncology, Ludwig Cancer Research Center, Epalinges, Switzerland.
8
Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.

Abstract

Antibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising target for immunotherapy. Indeed, BTLA inhibits T-cell proliferation and cytokine production. The crystal structure of the BTLA/HVEM complex has shown that the HVEM(26-38) fragment is directly involved in protein binding. We designed and analyzed the capacity of several analogs of this fragment to block the ligation between BTLA and HVEM, using competitive ELISA and cellular assay. We found that the HVEM(23-39) peptide can block BTLA/HVEM ligation. However, the blocking ability was due to the Cys encompassed in this peptide and that even free cysteine targeted the BTLA protein and blocked its interaction with HVEM. These data highlight a Cys-related artefact in vitro, which should be taken in consideration for future development of BTLA/HVEM blocking compounds.

PMID:
28594868
PMCID:
PMC5464627
DOI:
10.1371/journal.pone.0179201
[Indexed for MEDLINE]
Free PMC Article

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