CYTOKINE INDUCED KILLER CELLS AFTER AUTOLOGOUS/ALLOGENIC MARROW TRANSPLANTATION

Stanford University, Stanford CA

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Abstract

Hematopoietic cell transplantation has proven to be effective therapy for a number of hematologic malignancies. A major problem limiting success is relapse of the underlying malignancy. Despite this risk of relapse most patients achieve a state of minimal residual disease where immune interventions may prove to be effective. We have developed in vitro conditions resulting in the dramatic expansion of T cells which share functional and phenotypic properties with NK cells termed cytokine induced killer (CIK) cells. In this project we will explore several biological properties of both human and murine CIK cells. In particular, we will investigate the cell surface phenotype, expression of NK functional receptors and mechanism of cytolysis against tumor cell lines and fresh leukemic targets. We will explore the in vivo activity of CIK cells utilizing a novel quantitative, non-invasive tumor model system based upon the light emitting properties of luciferase transfectants. Using this system tumor growth can be rapidly and quantitatively assessed which will be used to characterize the cell populations in CIK cultures with in vivo function and to optimize CIK cell based immunotherapy. Using the same strategy CIK cells will be labeled and direct trafficking to the tumor visualized and optimized. We have previously demonstrated that CIK cells have markedly attenuated capacity for graft-vs-host disease (GVHD) induction in part due to the production of interferon-gamma. Using these in vivo models we will explore the mechanisms by which CIK cells retain graft-vs- leukemia (GVL) effects with reduced GVHD. CIK cells have a number of important properties making this cell population promising for the treatment of minimal residual disease in the post-translation setting. These include rapid expansion, broad in vitro and in vivo cytotoxic activity against hematopoietic malignancies, lack of requirement for infusional IL-2 and reduced capacity for GVHD induction. Our hypothesis is that by understanding the mechanisms of action of CIK cells strategies will be developed which will enhance the efficacy of autologous and allogeneic transplantation. In addition, basic insights into T cell biology, GVL and GVHD will be made.