Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD

Yi - Zeng, J. Stokes, S. Hahn, E. Hoffman, Emmanuel Katsanis

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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-. 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.

Original languageEnglish (US)
Pages (from-to)1076-1083
Number of pages8
JournalBone Marrow Transplantation
Volume49
Issue number8
DOIs
StatePublished - 2014

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Helper-Inducer T-Lymphocytes
Th1 Cells
Leukemia
Transplants
Cell Transplantation
Cell- and Tissue-Based Therapy
T-Lymphocytes
CD40 Ligand
Adoptive Transfer
Hematopoiesis
Tissue Donors
Survival

ASJC Scopus subject areas

  • Hematology
  • Transplantation
  • Medicine(all)

Cite this

Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD. / Zeng, Yi -; Stokes, J.; Hahn, S.; Hoffman, E.; Katsanis, Emmanuel.

In: Bone Marrow Transplantation, Vol. 49, No. 8, 2014, p. 1076-1083.

Research output: Contribution to journalArticle

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AU - Katsanis, Emmanuel

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