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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-03-0831.
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Blood, 15 March 2003, Vol. 101, No. 6, pp. 2300-2306
IMMUNOBIOLOGY
T-cell activation and cytokine production via a bispecific
single-chain antibody fragment targeted to blood-stage malaria
parasites
Shigeto Yoshida,
Tominari Kobayashi,
Hiroyuki Matsuoka,
Chisato Seki,
William L. Gosnell,
Sandra P. Chang, and
Akira Ishii
From the Department of Medical Zoology, Jichi Medical
School, Tochigi, Japan; and the Department of Tropical
Medicine and Medical Microbiology, John A. Burns School of Medicine,
Leahi Hospital, University of Hawaii at Manoa, Honolulu, HI.
A novel bispecific single-chain antibody fragment (biscFv) has been
constructed to address the possibility of a new approach to malaria
therapeutic drug development. The biscFv consists of 2 different
single-chain antibody fragments linked by a flexible peptide linker
(Gly4-Ser)3. Of the 2 scFv fragments,
one is directed against a conserved epitope of the 19-kDa C-terminal
fragment of the major surface protein of human malignant malaria
parasite, Plasmodium falciparum, and the other is directed
against the CD3 antigen of human T cells. The biscFv expressed
by a recombinant baculovirus retained the antigen-binding properties of
the corresponding univalent single-chain antibody fragments and
formed a bridge between P falciparum and T cells.
In cooperation with T cells, the biscFv specifically induced not only
interferon and tumor necrosis factor , but also a significant
increase of merozoite phagocytosis and growth inhibition of P
falciparum in vitro. Thus, the biscFv possesses highly
selective malaria-targeting properties and stimulates T cells to induce
cytokines, presumably resulting in activation of macrophages,
neutrophils, and natural killer cells, and parasite killing in vivo.

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