In vitro and in vivo assessment of the graft-versus-leukemia activity of cord blood

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Abstract

Allogeneic bone marrow transplantation (BMT) frequently is accompanied by the occurrence of graft-versus-host disease (GVHD). GVHD is thought to mediate a beneficial graft-versus-leukemia (GVL) effect believed to be important for disease-free survival in cancer patients. However, it is uncertain if GVHD and GVL are mediated by unique effector cell populations in the graft. The lack of bone marrow donors for individuals needing HLA-matched, unrelated BMT has recently led to the use of cord blood for transplantation. Cord blood transplantation has generated much enthusiasm because of its very low incidence of GVHD, even in HLA-mismatched situations, owing to intrinsic defects in mature T cell functions. Concerns have arisen, however, as to whether cord blood would mediate a significant GVL activity in vivo in the absence of GVHD, and thus prevent relapse in patients treated for malignancies. In this study in vitro and in vivo assessments have been made of the ability of cord blood to mediate GVL activity, focusing on non-specific effector cell mechanisms. Although minimal non-specific cytotoxic activity is found in freshly isolated cord blood (both NK and LAK cell activity), it is rapidly induced and displays a spectrum of lytic activity similar to adult peripheral blood. The kinetics of LAK cell induction in cord blood as well as the responsiveness to IL-2 stimulation was identical to adult peripheral blood. The induction of cord blood lytic activity was not the result of an expansion of NK cells, but rather was found to be related to the induction of LAK cell activity by NK cells and an expansion of CD8+ T cells with LAK cell activity. Significantly, cord blood was capable of purging contaminated cell cultures of tumor cells even in the absence of added IL-2. In a model system paralleling that of transplanted cancer patients, cord blood was able to cure the majority of SCID mice bearing human tumors. Thus, both in vitro and ill vivo cord blood appears quite capable of mediating a biologically significant GVL effect via NK and LAK cell activities, independent of T cell-mediated GVHD.

Original languageEnglish (US)
Pages (from-to)17-23
Number of pages7
JournalBone Marrow Transplantation
Volume15
Issue number1
StatePublished - Jan 1 1995

Keywords

  • Cord blood
  • GVL
  • In vitro
  • In vivo

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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