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Originally published In Press as doi:10.1074/jbc.C000573200 on September 6, 2000

J. Biol. Chem., Vol. 275, Issue 42, 32832-32836, October 20, 2000
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Biochemical Engineering of Surface alpha 2-8 Polysialic Acid for Immunotargeting Tumor Cells*

Tianmin Liu, Zhongwu Guo, Qingling Yang, Subash Sad, and Harold J. JenningsDagger

From the Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada

To target tumor cells for immunotherapy, we evaluated the feasibility of altering the epitopes on the surface polysialic acid of tumor cells. A precursor (N-propionylmannosamine), when incubated with leukemic cells, RBL-2H3 and RMA, resulted in substitution of the N-acetyl groups of surface alpha 2-8 polysialic acid with N-propionyl groups. Expression of the altered alpha 2-8 N-propionylpolysialic acid on the surface of tumor cells induced their susceptibility to cell death mediated by monoclonal antibody 13D9 (mAb 13D9), which specifically recognizes alpha 2-8 N-propionylated polysialic acid. The expression of alpha 2-8 N-propionylated polysialic acid and the lysis of tumor cells by antibody-dependent cytotoxicity depended on the time and dose of incorporation of N-propionylated mannosamine. In vivo, mAb 13D9 effectively controlled metastasis of leukemic cells RMA when mice were administered the precursor N-propionylated mannosamine.


* This is National Research Council of Canada publication number 42421.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. Tel.: 613-990-0821; Fax: 613-941-1327; E-mail: harry.jennings@nrc.ca.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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