CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia

• Main Authors: Carlos Cuesta-Mateos, Patricia Fuentes, Alexandra Schrader, Raquel Juárez-Sánchez, Javier Loscertales, Tamara Mateu-Albero, Lorena Vega-Piris, Marina Espartero-Santos, Ana Marcos-Jimenez, Blanca Andrea Sánchez-López, Yaiza Pérez-García, Dennis Jungherz, Sebastian Oberbeck, Linus Wahnschaffe, Anna Kreutzman, Emma I. Andersson, Satu Mustjoki, Edgar Faber, Ana Urzainqui, Manuel Fresno, Kostantino Stamatakis, Arantzazu Alfranca, Fernando Terrón, Marco Herling, María Luisa Toribio, Cecilia Muñoz-Calleja
• Format: Article
• Language: English
• Published: BMC 2020-10-01
• Series: Biomarker Research
• Subjects: CCR7; T-PLL; mAb; T-cell lymphomas; Immunotherapy
• Online Access: http://link.springer.com/article/10.1186/s40364-020-00234-z

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.