Abstract LB015: CCR7-expressing T-cell acute lymphoblastic leukemia mouse model provides a platform for developing novel anti-CCR7 therapies to prevent CNS invasion

Abstract

Abstract C-C chemokine receptor 7 (CCR7) plays a pivotal role in promoting the migration of T-cell acute lymphoblastic leukemia (T-ALL) cells into the central nervous system during leukemogenesis. Overexpression of CCR7 has also been linked to developing central nervous system (CNS) lymphoma. CCR7 and its ligand, CCL19 are important mediators in the development of these cancers. Thus there is an urgent need for a translational syngeneic CCR7-expressing T-ALL model that can speed up the discovery of drugs that can be used to block CCR7 function during the progression of T-ALL. Using the established ROSA26 floxed-stop Prdm14 (R26PR)/Mx-1 Cre mouse T-ALL model we have initiated studies using a CCR7/CCL19 antagonist, ELC8-83 to examine the molecular mechanisms that mediate CCR7-directed migration to, invasion of, proliferation within and exit from the CNS. mRNA expression of CCR7 in the T-ALL was confirmed by RT-PCR and protein expression on the cell surface was confirmed by flow cytometry. Chemotaxis and calcium mobilization of T-ALL in response to CCL19 was confirmed using transwell-migration assays and FURA-4. ELC8-83 was used to block this signaling. These studies demonstrate the efficacy of ELC8-83 in blocking signaling in T-ALL and provide a platform for testing ELC8-83 in the mouse model of T-ALL. Citation Format: Angel Torres, Aaron Vazquez, Sean Glenn, Zenaida Fuentes, jessica Chacon, Colin Bill, Charlotte M. Vines. CCR7-expressing T-cell acute lymphoblastic leukemia mouse model provides a platform for developing novel anti-CCR7 therapies to prevent CNS invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB015.