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Using mouse models, researchers have developed a new cellular programming approach to create alloreactive T cells they say eliminate leukemic cells without causing graft-versus-host disease (GVHD).
They created the T cells using the donor key immune cell. When used in allogeneic hematopoietic stem cell transplantation and anti-leukemia therapy, the new approach reduced the toxicities that cause GVHD while preserving the anti-leukemia activity of the immune cell.
“This approach will be useful in the future when developing novel methods for immunotherapy,” said Yi Zhang, MD, PhD, of Temple University in Philadelphia, Pennsylvania.
Dr Zhang and colleagues took murine bone marrow using Flt3 ligand and Toll-like receptor agonists to produce δ-like ligand 4-positive dendritic cells (Dll4hiDCs). When the dendritic cells were stimulated, CD4+ naïve T cells underwent effector differentiation and produced high levels of IFN-γ and IL-17 in vitro.
The team then transferred the allogeneic Dll4hiDC-induced T cells into the mice. The cells did not induce severe GVHD and preserved anti-leukemic activity, “significantly improving the survival of leukemic mice undergoing allogeneic HSCT,” they said.
They noted that the IFN-γ was important for Dll4hiDC programming in reducing the GVHD toxicities of alloreactive T cells. When the researchers transferred unstimulated T cells into mice, 5 of 8 mice died from GVHD and 3 of 8 died with tumor. Those that received Dll4hiDC-induced T cells did not develop GVHD.
They also emphasized that this platform does not require transfection with viral vectors, which has limitations of safety and efficiency.
“This system will not only be useful for reducing GvHD,” Dr Zhang said, “but can also be used in the identification of T cells for the improvement of other types of immunotherapy for advanced cancer.”
The team published this research in Blood. 
Using mouse models, researchers have developed a new cellular programming approach to create alloreactive T cells they say eliminate leukemic cells without causing graft-versus-host disease (GVHD).
They created the T cells using the donor key immune cell. When used in allogeneic hematopoietic stem cell transplantation and anti-leukemia therapy, the new approach reduced the toxicities that cause GVHD while preserving the anti-leukemia activity of the immune cell.
“This approach will be useful in the future when developing novel methods for immunotherapy,” said Yi Zhang, MD, PhD, of Temple University in Philadelphia, Pennsylvania.
Dr Zhang and colleagues took murine bone marrow using Flt3 ligand and Toll-like receptor agonists to produce δ-like ligand 4-positive dendritic cells (Dll4hiDCs). When the dendritic cells were stimulated, CD4+ naïve T cells underwent effector differentiation and produced high levels of IFN-γ and IL-17 in vitro.
The team then transferred the allogeneic Dll4hiDC-induced T cells into the mice. The cells did not induce severe GVHD and preserved anti-leukemic activity, “significantly improving the survival of leukemic mice undergoing allogeneic HSCT,” they said.
They noted that the IFN-γ was important for Dll4hiDC programming in reducing the GVHD toxicities of alloreactive T cells. When the researchers transferred unstimulated T cells into mice, 5 of 8 mice died from GVHD and 3 of 8 died with tumor. Those that received Dll4hiDC-induced T cells did not develop GVHD.
They also emphasized that this platform does not require transfection with viral vectors, which has limitations of safety and efficiency.
“This system will not only be useful for reducing GvHD,” Dr Zhang said, “but can also be used in the identification of T cells for the improvement of other types of immunotherapy for advanced cancer.”
The team published this research in Blood.
Using mouse models, researchers have developed a new cellular programming approach to create alloreactive T cells they say eliminate leukemic cells without causing graft-versus-host disease (GVHD).
They created the T cells using the donor key immune cell. When used in allogeneic hematopoietic stem cell transplantation and anti-leukemia therapy, the new approach reduced the toxicities that cause GVHD while preserving the anti-leukemia activity of the immune cell.
“This approach will be useful in the future when developing novel methods for immunotherapy,” said Yi Zhang, MD, PhD, of Temple University in Philadelphia, Pennsylvania.
Dr Zhang and colleagues took murine bone marrow using Flt3 ligand and Toll-like receptor agonists to produce δ-like ligand 4-positive dendritic cells (Dll4hiDCs). When the dendritic cells were stimulated, CD4+ naïve T cells underwent effector differentiation and produced high levels of IFN-γ and IL-17 in vitro.
The team then transferred the allogeneic Dll4hiDC-induced T cells into the mice. The cells did not induce severe GVHD and preserved anti-leukemic activity, “significantly improving the survival of leukemic mice undergoing allogeneic HSCT,” they said.
They noted that the IFN-γ was important for Dll4hiDC programming in reducing the GVHD toxicities of alloreactive T cells. When the researchers transferred unstimulated T cells into mice, 5 of 8 mice died from GVHD and 3 of 8 died with tumor. Those that received Dll4hiDC-induced T cells did not develop GVHD.
They also emphasized that this platform does not require transfection with viral vectors, which has limitations of safety and efficiency.
“This system will not only be useful for reducing GvHD,” Dr Zhang said, “but can also be used in the identification of T cells for the improvement of other types of immunotherapy for advanced cancer.”
The team published this research in Blood.