Abstract 33: Humanized MOLM-13 AML model as a versatile tool to study immune-activating agents

Abstract

Abstract Acute myeloid leukemia (AML) is the most common acute leukemia and second most common form of blood cancer in children and adolescents. Despite progress in understanding the biology of AML, therapeutic intervention plans have not changed nor outcomes significantly improved over the last years. Current AML treatment consists of intensive chemotherapy followed by stem cell transplantation. While initially many patients respond well to chemotherapy, relapse rates are high and still associated with poor prognosis. Evidence suggests that chemo-resistant leukemic stem cells (LSCs) have the ability to reinitiate and sustain the disease. Therefore, novel therapies are urgently needed to improve AML treatment and well-characterized in vivo models modelling this disease are a prerequisite for improving the current state. At Reaction Biology, we have used NOG and NOD-SCID mice to establish a humanized MOLM-13 AML model concomitantly engrafted with human T cells. Luciferase positive MOLM-13_Luc AML cells were injected both in naïve mice and mice pre-treated with Cyclophosphamide. Thereafter, tumor growth was monitored by bioluminescence measurements to track disseminated tumor burden and isolated T cells were applied upon tumor growth detection (generally observed on day 8 or 15 post-tumor cell inoculation for NOG or NOD-SCID mice, respectively). For each of the inoculations, fresh T cells were obtained by negative selection from buffy coat derived PBMCs with a purity of >95 %. Following administration of human T cells, animals were monitored daily, including the collection of animal weights (3x/w), and tumor burden (2x/w) via in vivo bioluminescence imaging technique. MOLM-13_Luc tumor cells grew rapidly in all NOG mice with termination of the last animals as early as day 17. Neither Cyclophosphamide pre-treatment, nor the addition of T cells influenced tumor growth or prolonged survival. In Cyclophosphamide pre-treated NOD-SCID mice, onset of tumor growth was observed to initiate homogenously at day 13 post inoculation (with applied T cells being ineffective in reducing tumor burden), whereas tumor growth in non-pre-treated animals was heterogenous and delayed by more than 7d. The presence of T cells affected tumor growth even further. Beside T cell addition, also the application of NK cell therapies were successfully investigated (data not shown). Taken together, the MOLM-13_Luc AML tumor model is found to be suitable for the investigation of bi-specific engagers using isolated T or NK cells. Citation Format: Carla Castro, Philipp Metzger, Cynthia Obodozie, Holger Weber. Humanized MOLM-13 AML model as a versatile tool to study immune-activating agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 33.