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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. 

Abstract Our understanding of the tectonic development of the African continent and the interplay between its geological provinces is hindered by unevenly distributed seismic instrumentation. In order to better understand the continent, we used long‐period ambient noise full‐waveform tomography on data collected from 186 broadband seismic stations throughout Africa and surrounding regions to better image the upper mantle structure. We extracted empirical Green's functions from ambient seismic noise using a frequency‐time normalization method and retrieved coherent signal at periods of 7–340 s. We simulated wave propagation through a heterogeneous Earth using a spherical finite‐difference approach to obtain synthetic waveforms, measured the misfit as phase delay between the data and synthetics, calculated numerical sensitivity kernels using the scattering integral approach, and iteratively inverted for structure. The resulting images of isotropic, shear wave speed for the continent reveal segmented, low‐velocity upper mantle beneath the highly magmatic northern and eastern sections of the East African Rift System (EARS). In the southern and western sections, high‐velocity upper mantle dominates, and distinct, low‐velocity anomalies are restricted to regions of current volcanism. At deeper depths, the southern and western EARS transition to low velocities. In addition to the EARS, several low‐velocity anomalies are scattered through the shallow upper mantle beneath Angola and North Africa, and some of these low‐velocity anomalies may be connected to a deeper feature. Distinct upper mantle high‐velocity anomalies are imaged throughout the continent and suggest multiple cratonic roots within the Congo region and possible cratonic roots within the Sahara Metacraton.