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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1999-2001
BRIEF REPORT
Chimeric Fv- or Fv- receptors are not sufficient to
induce activation or cytokine production in peripheral T
cells
Thomas Brocker
From the Institute for Biology III, Department of
Molecular Immunology at the Max-Planck-Institute for Immunobiology, and
Basel Institute for Immunology, Basel, Switzerland.
In current clinical trials, chimeric antibody-like receptors
fused to signaling domains derived from TCR- or Fc( )RI -chain are tested for their ability to lyse tumor cells in vivo. In this study, the function of primary T cells expressing such receptors has
been investigated in transgenic mice. These receptors cannot induce
proliferation of resting T cells or trigger the production of optimal
amounts of cytokines. It is further demonstrated that an initial low
presence of cytokine message and protein is disappearing rather fast,
whereas the triggering of endogenous TCR/CD3 in the same cells leads to
normal prolonged cytokine production. The direct clinical relevance of
these findings is further underlined by the increased in vivo tumor
rejection by T cells expressing chimeric receptors in presence of
exogenous interleukin-2. Therefore, adoptive T-cell therapy using
primary T cells transfected with single chain receptors might benefit
substantially from the accompanying administration of cytokines.
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