Cancer Institute A national cancer institute
designated cancer center

Robert Negrin

Publication Details

  • Engineering hematopoietic grafts: Purified allogeneic hematopoietic stem cells plus expanded CD8(+) NK-T cells in the treatment of lymphoma BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Verneris, M. R., Ito, M., Baker, E., Arshi, A., Negrin, R. S., Shizuru, J. A. 2001; 7 (10): 532-542

    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-y, 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.

    View details for Web of Science ID 000172275500002

    View details for PubMedID 11760085

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