Studies of ex vivo activated and expanded CD8+ NK-T cells in humans and mice

Adoptive cellular therapy holds promise for improving the outcome of hematopoietic cell transplantation (HCT). At present, donor lymphocyte infusion post-HCT is efficacious for only a limited number of diseases, yet can induce significant graft versus host disease (GVHD). To improve the outcome of t...

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Bibliographic Details
Published in:Journal of clinical immunology 2002-05, Vol.22 (3), p.131-136
Main Authors: VERNERIS, Michael R, BAKER, Jeanette, EDINGER, Matthias, NEGRIN, Robert S
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
Biological and medical sciences
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cell Culture Techniques - methods
Hematologic Neoplasms - therapy
Humans
Immunotherapy, Adoptive - methods
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
Lymphocyte Activation - immunology
Medical sciences
Mice
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
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Summary:Adoptive cellular therapy holds promise for improving the outcome of hematopoietic cell transplantation (HCT). At present, donor lymphocyte infusion post-HCT is efficacious for only a limited number of diseases, yet can induce significant graft versus host disease (GVHD). To improve the outcome of this approach, it would be beneficial to identify populations of T cells that retain graft versus tumor (GVT) effects with reduced propensity for GVHD. Here we describe studies of both human and murine expanded CIK cells or CD8+ NK-T cells. These related populations of cells are ex vivo activated and expanded T cells that express both T and NK markers. They can be generated from patients with malignancies and mediate cytotoxicity against autologous hematopoietic malignancies. Recent work in murine models show that these cells mediate cytotoxicity by using a perforin-granzyme and not through Fas ligand. In allogeneic stem cell transplantation experiments, large numbers of expanded CD8+ NK-T cells could be transplanted across major histocompatibility barriers without causing severe GVHD and GVT effects were retained. We conclude that expanded CD8+ NK-T cells are a promising form of cellular therapy in the allogeneic setting.
ISSN:0271-9142
1573-2592
DOI:10.1023/a:1015415928521