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Clinical Cooperation Group "Bispecific Antibodies," Department of Otorhinolaryngology, Ludwig-Maximilians-University, Munich, Germany; and
Institutes of Clinical Molecular Biology and Tumor Genetics and Experimental Hematology, Gesellschaft für Strahlung und Umweltforschung-National Research Center for Environment and Health, Munich, Germany
Bispecific Abs (bsAb) are promising immunological tools for the
elimination of tumor cells in minimal residual disease situations. In
principle, they target an Ag on tumor cells and recruit one class of
effector cell. Because immune reactions in vivo are more complex and
are mediated by different classes of effector cell, we argue that
conventional bsAb might not yield optimal immune responses at the tumor
site. We therefore constructed a bsAb that combines the two potent
effector subclasses mouse IgG2a and rat IgG2b. This bispecific molecule
not only recruits T cells via its one binding arm, but simultaneously
activates Fc
R+ accessory cells via its Fc region. We
demonstrate here that the activation of both T lymphocytes and
accessory cells leads to production of immunomodulating cytokines like
IL-1
, IL-2, IL-6, IL-12, and DC-CK1. Thus this new class of bsAb
elicits excellent antitumor activity in vitro even without the addition
of exogenous IL-2, and therefore represents a totally self-supporting
system.
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