Table 2. Preclinical observations based on ex vivo Notch ligand-mediated expansion of T cell progenitors.
Cell source | Notch ligand source | Key Observation(s) | Reference |
---|---|---|---|
Mouse BM LSKs | OP9-Delta-like1 cells | Delta-like1 expands DN2 and DN3 pre-T cells Expanded pre-T cells increase thymic engraftment, bacterial clearance, and have NK-independent GVT effects |
Zakrzewski et al., 2006 81 |
Mouse BM LSKs | Immobilized Delta-1ext-IgG | Expansion of DN2 pre-T cells correlates with Delta-like1 density Expanded pre-T cells engraft the thymus and produce mature T cells |
Dallas et al., 2007 68 |
Mouse BM LSKs | OP9-Delta-like1 cells | Expanded pre-T cells induce GVT, but not GVHD, and have potential for anti-tumor engineering | Zakrzewski et al., 2008 82 |
Human UCB: CD34+ cells | OP9-Delta-like1 cells | Expanded pre-T cells engraft the thymus and produce mature T cells | Awong et al., 2009 83 |
Mouse BM LSKs | OP9-Delta-like1 cells | Expanded pre-T cells engraft extra-thymically, producing mature T cells | Holland et al., 2012 84 |
BM, bone marrow; LSK, Lin-Sca-1+c-Kit+ hematopoietic stem and progenitor cells; GVT, graft-versus-tumor; GVHD, graft-versus-host disease; Ag, antigen; UCB, umbilical cord blood.