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DOI: 10.3791/68013-v
Kun Yun1,2,3, R. Leo Sakemura1,4, Truc N. Huynh1,4, Brooke Kimball1,4, Elizabeth Siegler1,4, Saad S. Kenderian1,2,3,4,5
1T Cell Engineering,Mayo Clinic, 2Department of Molecular Medicine,Mayo Clinic, 3Mayo Clinic Graduate School of Biomedical Sciences, 4Division of Hematology,Mayo Clinic, 5Department of Immunology,Mayo Clinic
Given the limited xenograft models available to study interactions between human CART and myeloid cells, we established in vitro and in vivo models to understand the impacts of human macrophages on CART cells. Findings can potentially be generalized to evaluate macrophage roles in the tumor microenvironment and test macrophage-targeted immunotherapies.
Our study provides simplified in vitro and in vivo models to understand the impact of human immunosuppressive macrophages on CA 19 anti-tumor activity in the context of mantle cell lymphoma. The most commonly used model to study the human macrophages and monocytes in vivo is to engraft hematopoietic stem cells into eradicated immunodeficient mice. Engrafting immunodeficient mice with human hematopoietic stem cells to study human myeloid cells in mice can be time-consuming and expensive.
The engraftment efficiency can be limited as well. We establish more simplified in vitro and in vivo models to study interactions between human macrophages, CAR T, and tumor cells. It can be used to test other macrophage-targeted immunotherapies as well.
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