Abstract
Solid tumors contain abnormal physical and biochemical barriers that hinder chimeric antigen receptor (CAR) T cell therapies. However, there is a lack of understanding on how the solid tumor microenvironment (e.g. hypoxia) modulates CAR-T cell function. Hypoxia is a common feature of many advanced solid tumors that contributes to reprogramming of cancer and T cell metabolism as well as their phenotypes and interactions. To gain insights into the activities of CAR-T cells in solid tumors and to assess the effectiveness of new combination treatments involving CAR-T cells, in vitro models that faithfully reflect CAR-T cell–solid tumor interactions under physiologically relevant tumor microenvironment is needed. Here we demonstrate how to establish a hypoxic 3-dimensional (3-D) tumor model using a cleanroom-free, micromilling-based microdevice and assess the efficacy of the combination treatment with CAR-T cells and PD-1/PD-L1 inhibition.
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Acknowledgement
This work was supported by an NIH National Cancer Institute grant (R01CA220012), a STOP CANCER Marni Levine Memorial Research Career Development Award, the USC Viterbi School of Engineering, and the USC Provost’s PhD Fellowship. This research was also supported by shared resources from an NIH National Cancer Institute Award (P30CA014089).
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Oh, J.M., Shen, K. (2024). Hypoxic 3D Tumor Model for Evaluating of CAR-T Cell Therapy In Vitro. In: Siciliano, V., Ceroni, F. (eds) Cancer Immunotherapy. Methods in Molecular Biology, vol 2748. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3593-3_10
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DOI: https://doi.org/10.1007/978-1-0716-3593-3_10
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