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Clin Exp Immunol. 1997 May;108(2):352-7.

Specific activation of resting T cells against tumour cells by bispecific antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation and recruitment of MHC-independent cytotoxicity.

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1
Klinik I für Innere Medizin der Universität zu Köln, Germany.

Abstract

Specific activation of resting lymphocytes for tumour targeting can be achieved by bispecific monoclonal antibodies (bi-MoAbs) with specificity for tumour antigens and T cell-activating antigens in combination with a costimulatory anti-CD28 antibody. In this study we focus on the immunomodulatory function of an anti-CD3/CA19-9 bi-MoAb in combination with a costimulatory anti-CD28 antibody which may result not only in antigen-specific, T cell-mediated tumour cell lysis but also in recruitment of other cellular effector functions. In combination with costimulatory anti-CD28 antibodies, resting peripheral lymphocytes could be activated specifically to secrete high amounts of Th1 cytokines (IL-2, interferon-gamma (IFN-gamma)) characterizing a cellular immune response. In contrast, no IL-4 and only low amounts of IL-10 could be detected. Furthermore, bi-MoAb-mediated CA19-9-specific activation of T cells was accompanied by recruitment of MHC- and CA19-9-independent cytotoxicity, as was determined by lysis of different CA19-9-cell lines. This MHC-independent cytotxicity was mediated at least in part by activated natural killer (NK) cells, as depletion of CD16+ NK cells resulted in substantial decrease of cytotoxicity against CA19-9- targets. Our results indicate that specific activation of resting T cells with CD3-associated bi-MoAbs in combination with an anti-CD28 antibody leads to a Th1 differentiation pathway and is accompanied by recruitment of MHC-independent lymphokine-activated killer (LAK) cell cytotoxicity which can possibly be directed against a heterogeneous tumour.

PMID:
9158110
PMCID:
PMC1904656
[Indexed for MEDLINE]
Free PMC Article
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