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Updated: Aug 14, 2026
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
Chimeric Fv-zeta or Fv-epsilon receptors are not sufficient to induce activation or cytokine production in peripheral
1Institute for Biology III, Department of Molecular Immunology at the Max-Planck-Institute for Immunobiology, Basel, Switzerland. tbrocker@gmx.de
Abstract:
In current clinical trials, chimeric antibody-like receptors fused to signaling domains derived from TCR-zeta or Fc(epsilon)RIgamma-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. (Blood. 2000;96:1999-2001)
Insights
Primary T cells with chimeric receptors show limited tumor cell lysis and cytokine production. Supplementing with interleukin-2 enhances tumor rejection, suggesting cytokine support is crucial for adoptive T-cell therapy.
Area of Science:
- Immunology
- Cancer Biology
- Cell Therapy
Background:
- Chimeric receptors are being tested in clinical trials for tumor cell lysis.
- These receptors are fused to signaling domains like TCR-zeta or Fc(epsilon)RIgamma.
Purpose of the Study:
- Investigate the function of primary T cells expressing chimeric receptors.
- Assess the potential of these T cells in adoptive T-cell therapy.
Main Methods:
- Transgenic mice models were used to study primary T cells.
- Functional assays assessed T cell proliferation, cytokine production, and tumor cell lysis.
Main Results:
- Chimeric receptors did not induce resting T cell proliferation or optimal cytokine production.
- Cytokine production was transient, unlike that from endogenous TCR/CD3 triggering.
- Exogenous interleukin-2 significantly increased in vivo tumor rejection by T cells.
Conclusions:
- Primary T cells with chimeric receptors have limitations in proliferation and cytokine signaling.
- Adoptive T-cell therapy may require concurrent cytokine administration for efficacy.
- Interleukin-2 supplementation is beneficial for enhancing chimeric receptor T-cell therapy against tumors.
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