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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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Submitted March 18, 2002
Accepted October 28, 2002

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

Department of Medical Zoology, Jichi Medical School, Tochigi, Japan
Department of Tropical Medicine and Medical Microbiology, University of Hawaii, Honolulu, HI, USA

* Corresponding author; email: shigeto{at}jichi.ac.jp.

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 two different single-chain antibody fragments linked by a flexible peptide linker (Gly4-Ser)3. One of the two scFv fragments 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 IFN-{gamma} and TNF-{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 NK cells and parasite killing in vivo.


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