Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD.
DLI is traditionally used to provide graft-versus-leukemia (GvL) effects when given to patients relapsing post-hematopoietic cell transplantation (HCT). However, it is often associated with significant GvHD and has only modest efficacy against acute leukemias. Therefore, novel cellular therapies are needed to improve the outcome of high-risk or relapsed leukemia patients following HCT. Activated T helper-1 (aTh-1) lymphocytes are CD4(+)CD25(+)CD40L(+)CD62L(lo) effector memory cells that produce large amounts of IFN-γ and TNF-α. We demonstrate that post-transplant adoptive aTh-1 cell therapy enhances GvL with limited GvHD in an MHC-mismatched murine BMT model. aTh-1 infusions result in superior leukemia-free survival when compared with unstimulated splenocytes (SC), purified CD4(+) T-cells and T-cell-enriched SC. aTh-1 cells display cytotoxicity against A20 leukemia cells in vitro and persist in vivo for at least 2 months following adoptive transfer. Furthermore, in contrast to unstimulated SC, aTh-1 cell infusion is associated with only transient, mild suppression of donor-derived hematopoiesis. aTh-1 cell therapy is safe, effective and warrants further investigation as an alternative to DLI.
Department of Pediatrics, Steele Children's Research Center, The University of Arizona, Tucson, AZ, USA.
Y
Y
Zeng
Department of Pediatrics, Steele Children's Research Center, The University of Arizona, Tucson, AZ, USA.
J
J
Stokes
Department of Pediatrics, Steele Children's Research Center, The University of Arizona, Tucson, AZ, USA.
S
S
Hahn
Department of Pediatrics, Steele Children's Research Center, The University of Arizona, Tucson, AZ, USA.
E
E
Hoffman
1] Department of Pediatrics, Steele Children's Research Center, The University of Arizona, Tucson, AZ, USA [2] Department of Immunobiology, The University of Arizona, Tucson, AZ, USA.
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0000000314666965
E
Katsanis
D064591:Allografts; D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D020544:Graft vs Leukemia Effect; D007938:Leukemia / Q000628:therapy*; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000637:transplantation*