Abstract
A major benefit of allogeneic hematopoietic cell transplantation (HCT) in the treatment of malignancies is the graft-versus-tumor (GVT) effect conferred by lymphocytes contained within the graft. However, lymphocytes can also induce the potentially lethal complication of graft-versus-host disease (GVHD). We have previously reported a method of generating large numbers of ex vivo activated and expanded T cells with antitumor activity after culture with interferon-γ, cross-linking antibodies to CD3, and interleukin-2. Murine splenocytes expanded under these conditions are a heterogeneous population of which approximately 20% to 60% of cells express natural killer (NK)-cell markers (NK1.1 and DX5) and display major histocompatibility complex (MHC)-unrestricted antitumor activity. Here we demonstrate the in vivo antitumor activity of this population of expanded CD8+ NK-T cells when transplanted across MHC barriers into tumor-bearing hosts. In cotransfer studies with purified allogeneic hematopoietic stem cells, expanded CD8+ NK-T cells confer GVT activity with minimal to no GVHD. In vitro studies show that, although expanded NK-T cells lyse normal allogeneic bone marrow cells, they preferentially mediate cytolysis against tumor targets. These cells persist in the peripheral circulation of host animals for at least 3 weeks posttransfer. GVT activity is dependent on perforin, but not on Fas-ligand. We conclude that expanded CD8+ NK-T cells may serve as a valuable adjuvant population for allogeneic HCT because they mediate GVT effects with minimal GVHD.
Original language | English (US) |
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Pages (from-to) | 532-542 |
Number of pages | 11 |
Journal | Biology of Blood and Marrow Transplantation |
Volume | 7 |
Issue number | 10 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by NIH grant CA8006-01 (R.S.N.), NCI grant CA49605 (R.S.N. and J.A.S.), the American Society of Hematology (M.R.V.), and the Burroughs Welcome Fund (J.A.S.).
Keywords
- Expanded CD8 NK-T cells
- GVHD
- Graft-versus-tumor effect
- Hematopoietic cell transplantation
- Hematopoietic stem cell
- Lymphoma
- Mice