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Title: Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma
Background: Glioblastoma (GBM) is an aggressive brain tumor giving a poor prognosis with the current treatment options. The advent of chimeric antigen receptor (CAR) T-cell therapy revolutionized the field of immunotherapy and has provided a new set of therapeutic options for refractory blood cancers. In an effort to apply this therapeutic approach to solid tumors, various immune cell types and CAR constructs are being studied. Notably, macrophages have recently emerged as potential candidates for targeting solid tumors, attributed to their inherent tumorinfiltrating capacity and abundant presence in the tumor microenvironment. Materials and methods: In this study, we developed a chemically defined differentiation protocol to generate macrophages from human pluripotent stem cells (hPSCs). A GBM-specific CAR was genetically incorporated into hPSCs to generate CAR hPSC-derived macrophages. Results: The CAR hPSC-derived macrophages exhibited potent anticancer activity against GBM cells in vitro. Conclusion: Our findings demonstrate the feasibility of generating functional CAR-macrophages from hPSCs for adoptive immunotherapy, thereby opening new avenues for the treatment of solid tumors, particularly GBM.  more » « less
Award ID(s):
2143064
NSF-PAR ID:
10490398
Author(s) / Creator(s):
; ;
Publisher / Repository:
Elsevier
Date Published:
Journal Name:
Immuno-Oncology and Technology
Volume:
20
Issue:
C
ISSN:
2590-0188
Page Range / eLocation ID:
100409
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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