Cuesta-Mateos, Carlo, Fuentes, Patricia ORCID: 0000-0003-4597-1022, Schrader, Alexandra, Juarez-Sanchez, Raquel, Loscertales, Javier, Mateu-Albero, Tamara, Vega-Piris, Lorena, Espartero-Santos, Marina, Marcos-Jimenez, Ana, Sanchez-Lopez, Blanca Andrea, Perez-Garcia, Yaiza, Jungherz, Dennis, Oberbeck, Sebastian, Wahnschaffe, Linus, Kreutzman, Anna, Andersson, Emma I., Mustjoki, Satu ORCID: 0000-0002-0816-8241, Faber, Edgar, Urzainqui, Ana, Fresno, Manuel, Stamatakis, Kostantino, Alfranca, Arantzazu ORCID: 0000-0002-3732-5816, Terron, Fernando, Herling, Marco, Toribio, Maria Luisa and Munoz-Calleja, Cecilia (2020). CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia. Biomark. Res., 8 (1). LONDON: BMC. ISSN 2050-7771

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Abstract

T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cuesta-Mateos, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuentes, PatriciaUNSPECIFIEDorcid.org/0000-0003-4597-1022UNSPECIFIED
Schrader, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juarez-Sanchez, RaquelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loscertales, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mateu-Albero, TamaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vega-Piris, LorenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espartero-Santos, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marcos-Jimenez, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Lopez, Blanca AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez-Garcia, YaizaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jungherz, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oberbeck, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wahnschaffe, LinusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreutzman, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andersson, Emma I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mustjoki, SatuUNSPECIFIEDorcid.org/0000-0002-0816-8241UNSPECIFIED
Faber, EdgarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Urzainqui, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fresno, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stamatakis, KostantinoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alfranca, ArantzazuUNSPECIFIEDorcid.org/0000-0002-3732-5816UNSPECIFIED
Terron, FernandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herling, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toribio, Maria LuisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munoz-Calleja, CeciliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-314378
DOI: 10.1186/s40364-020-00234-z
Journal or Publication Title: Biomark. Res.
Volume: 8
Number: 1
Date: 2020
Publisher: BMC
Place of Publication: LONDON
ISSN: 2050-7771
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOKINE RECEPTORS; EXPRESSION; ALEMTUZUMAB; INFILTRATION; MIGRATION; KINASE; CD52; SKIN; CHEMOIMMUNOTHERAPYMultiple languages
Oncology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31437

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