Chimeric Fv-xi or Fv-epsilon receptors are not sufficient to induce activation or cytokine production in peripheral T cells

In current clinical trials, chimeric antibody-like receptors fused to signa ling domains derived from TCR-zeta or Fc(epsilon)RI gamma-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 trans genic mice. These receptors cannot induce proliferation of resting T cells or trigger the production of optimal amounts of cytokines. It is further de monstrated that an initial low presence of cytokine message and protein is disappearing rather fast, whereas the triggering of endogenous TCR/CD3 in t he same cells leads to normal prolonged cytokine production. The direct cli nical 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 primar y T cells transfected with single chain receptors might benefit substantial ly from the accompanying administration of cytokines, (C) 2000 by The American Society of Hematology.