Abstract LB269: Inhibition Of C-C chemokine receptor 7 extends survival rate in murine model of T-cell acute lymphoblastic leukemia

Abstract

Abstract C-C Chemokine Receptor 7 (CCR7) expression in pediatric T-cell acute lymphoblastic leukemia (T-ALL) promotes entry of leukemic cells into the central nervous system (CNS), where the disease finds sanctuary from systemic chemotherapies. To confirm that Notch1 drives expression of CCR7, we modified the ROSA26-PRDM14 ([PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ (retinoblastoma interacting zinc finger) homology domain containing 14]) MX-1 Cre inducible CD8+ T-ALL mouse model. This model, upon induction with polyI:C, expresses NOTCH1 downstream of PRDM14, and the T-ALL cells enter the CNS during leukemogenesis. We crossed these mice with ROSA26-Luc2 mice, which allows for tracking of T-ALL cells during disease progression. We questioned if these T-ALL cells expressed CCR7. We found that not only do the T-ALL cells express CCR7 and enter the CNS, but that a CCR7 antagonist, CCL198-83 administered during leukemogenesis doubles the mean survival of the CCL198-83 treated mice from 45 to 90 days. These studies provide a novel platform for a potential therapeutic that can be used to limit CNS entry and potentially recycling through the CNS. Citation Format: Anahi Sanchez, Aaron E. Vazquez, Janet M. Valenzuela, Savannah Stanley, Colin A. Bill, Charlotte M. Vines. Inhibition Of C-C chemokine receptor 7 extends survival rate in murine model of T-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB269.