Abstract LB-137: Three-dimensional cytotoxicity assay using magnetic 3D bioprinting for measuring CAR T cell function in heterogeneous solid tumor microenvironments
Year: 2019
Type: conference-abstract
Abstract: Chromium release assays are routinely utilized to assess cytotoxic activity and function of tumor targeting T cells expressing chimeric antigen receptors (CAR T cells). Although these assays can predict the activity of CAR T cells targeting hematological malignancies, results of such assays do not accurately reflect the limited efficacy of T cell therapy observed against solid tumors. This limitation may be due to the disparity between the in vitro cell culture setting and the complex nature of solid tumor microenvironments and their vascular structure. To this end, we have developed a cytotoxicity assay based on a three-dimensional (3D) cell culture model, facilitated by magnetic 3D bioprinting, to more precisely mimic the complexity of solid tumor microenvironments in vitro. This model can be customized to reflect the heterogeneity of solid tumors by incorporating multiple cell types and immune cells. In these studies, we have demonstrated the feasibility of this assay using CD19-specific CAR T cells specifically targeting CD19+ leukemia cells in a heterogeneous 3D cell culture. We also show the CAR T cells infiltrating and targeting glioblastoma (U87) 3D cultures in real-time with fluorescence microscopy. Incorporation of this assay as a routine cytotoxicity assay will provide new dimensions to rapid immune function assessments by revealing the kinetics of cell killing through time-lapse microscopy, the persistence and targeting patterns of CAR T cells, and cell-specific killing by multicolor fluorescence imaging. This assay is being adapted into a 96-, 384- and 1,536-well formats for high-throughput applications.Citation Format: Glauco R. Souza, Amer Najjar. Three-dimensional cytotoxicity assay using magnetic 3D bioprinting for measuring CAR T cell function in heterogeneous solid tumor microenvironments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-137.
Source: Tumor Biology
Authors: Glauco R. Souza, Amer Najjar
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W2956119131