Search Results (1)

Humanized mice generated by hematopoietic stem cell (HSC) transplantation are limited by the immune system developed being allogeneic to the tumor. We have innovated a platform to reconstitute an autologous human immune system (HIS) in immunodeficient NOG-EXL mice from mobilized peripheral blood (MPB)-CD34 cells, along with PDX generated from the same patient’s tumor tissue. Patients consented under an IRB-approved protocol for tumor biopsy and HSC apheresis at Emory University. HSC collection included mobilization with G-CSF and plerixafor, immunomagnetic bead isolation with CliniMACS, and cryopreservation of CD34⁺ cells. PDX were established from biopsies or surgical specimens by passaging into immunodeficient mice. Irradiated NOG-EXL mice were engrafted with HSCs by intravenous transplantation of CD34⁺ HSC. Engraftment of human T cells, B cells, and myeloid cells in peripheral blood was assessed by serial flow cytometry of blood samples, with final assessment of immune components in spleen and bone marrow at 30 weeks. Twenty-eight PDX models were generated from 43 patients with HNSCC; 1 patient underwent apheresis. HSC engraftment in blood was observed in 100% of NOG-EXL mice at 8 weeks post-transplant, with 5–20% hCD45⁺ cells present in the periphery. B-cell development was predominant at early time points and declined over time. Human T-cell and subset development of CD4⁺ and CD8⁺ T cells were observed in blood from 15 weeks post-transplant. Strong development of the myeloid lineage (CD33⁺) was observed starting at 8 weeks and persisted throughout the study. These data demonstrate that mobilization and apheresis of HNSCC patients is technically and clinically feasible and may allow the establishment of autologous HIS-PDX mice. Full article