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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 gamma  and tumor necrosis factor alpha , 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.

© 2003 by The American Society of Hematology.
 

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