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Blood, 15 October 2001, Vol. 98, No. 8, pp. 2526-2534
NEOPLASIA
Induction of a long-lasting antitumor immunity by a trifunctional
bispecific antibody
Peter Ruf and
Horst Lindhofer
From the Clinical Cooperation Group Bispecific
Antibodies of the Department of Otorhinolaryngology, Ludwig Maximilians
University, Munich, Germany; and GSF Institute of Clinical Molecular
Biology and Tumor Genetics, National Research Center for Environment
and Health, Munich, Germany.
Bispecific antibodies (bsAbs) can efficiently mediate tumor cell
killing by redirecting preactivated or costimulated T cells to
disseminated tumor cells, especially in a minimal residual disease
situation. This study demonstrates that the trifunctional bsAb BiLu is
able to kill tumor cells very efficiently without any additional
costimulation of effector cells in vitro and in vivo. Remarkably, this
bsAb also induces a long-lasting protective immunity against the
targeted syngeneic mouse tumors (B16 melanoma and A20 B-cell lymphoma,
respectively). A strong correlation was observed between the induction
of a humoral immune response with tumor-reactive antibodies and the
survival of mice. This humoral response was at least in part tumor
specific as shown in the A20 model by the detection of induced
anti-idiotype antibodies. Both the survival of mice and antitumor
titers were significantly diminished when F(ab')2 fragments
of the same bsAb were applied, demonstrating the importance of the Fc
region in this process. With the use of T-cell depletion, a
contribution of a cellular antitumor response could be demonstrated.
These results reveal the necessity of the Fc region of the bsAb with
its potent immunoglobulin subclass combination mouse immunoglobulin G2a
(IgG2a) and rat IgG2b. The antigen-presenting system seems to be
crucial for achieving an efficient tumor cell killing and induction of
long-lasting antitumor immunity. Hereby, the recruitment and activation
of accessory cells by the intact bsAb is essential.
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