S15-DKO: New Platform for Engraftment of PBMC Supporting Multilineage Immune Cells and Low GvHD

Summary

Engraftment of immunodeficient NSG mice with human PBMC provides a robust platform for in vivo immunomodulation of human T cells. The ability to perform studies with co-engrafted human tumors is limited by the rapid development of xenogeneic graft-versus-host disease (xGvHD). This challenge was overcome by the development of the NSG-MHC I/II DKO mouse, an NSG variant devoid of expression of mouse MHC class I & II. This strain enables co-engraftment of human PBMC and tumors while maintaining body weight and overall health, allowing immuno-oncology studies for 40 days or longer, depending on the donor used. However, human immune cell engraftment remains dominated by CD4 and CD8 T cells. In order to expand engraftment of a broader array of immune cells following PBMC engraftment, the NSG-SGM3-IL15 strain was crossed to NSG-MHC I/II DKO, creating S15-DKO. Strain S15-DKO expresses human SCF, GM-CSF, IL-3, and IL-15 and lacks expression of MHC I and II. Following human PBMC engraftment, these mice lack acute xGvHD and support T cells plus an array of B cells, including plasma cells, as well as NK cells, cDC, macrophages, and γδ T cells.

Join us to review the engraftment profiles of multiple human PBMC donors in blood and tissues of the new S15-DKO recipient strain as well as data demonstrating memory B cell immune responses and NK cell functionality

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