Glioma tropism of lentivirally transduced hematopoietic progenitor cells

Abstract

Abstract. Experimental gliomas attract hematopoietic progenitor cells (HPC) in vivo. HPC are therefore promising candidates for a cell-based delivery of therapeutic molecules to experimental gliomas. A therapeutic application requires efficient genetic manipulation of the cellular vector and a lack of tumorigenicity. Here, we studied the impact of lentiviral transduction on the glioma tropism of human or murine HPC. Transduction of human or murine HPC with a GFP lentivirus (lenti-GFP) did not interfere with the gliomamediated attraction of HPC. Bone marrow reconstitution of C57Bl/6 mice with syngeneic GFP-transgenic lineagedepleted bone marrow cells (lin -BM) was as efficient as reconstitution with syngeneic lin -BM transduced ex vivo with lenti-GFP. SMA-560 gliomas growing orthotopically in lenti-GFP-reconstituted VM/Dk mice recruited GFP-positive bone marrow-derived cells. Thus, lentiviral transduction did not interfere with the attraction of exogenously injected HPC or endogenous bone marrow-derived cells by experimental gliomas. Lenti-GFP-HPC implanted directly into tumor-free brains were not tumorigenic. The intravenous injection of lenti-GFP-HPC in glioma-bearing mice did not alter the survival of otherwise untreated animals and had no impact on the survival benefit conferred by cerebral irradiation. Taken together, genetic manipulation of HPC with lenti-GFP neither made these cells tumorigenic nor interfered with their glioma tropism.

Targeting CSF1R Alone or in Combination with PD1 in Experimental Glioma

“…Five thousand SMA-560 cells were implanted as described previously [ 38 , 39 ]. In brief, adult mice were anesthetized with 3-component anesthesia (fentanyl, midazolam, and medetomidin) before intracranial injection to the right striatum using a fixed stereotactic apparatus.…”