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J. Biol. Chem., Vol. 275, Issue 42, 32832-32836, October 20, 2000
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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
Biochemical Engineering of Surface
2-8 Polysialic Acid for
Immunotargeting Tumor Cells*
2-8 polysialic acid with
N-propionyl groups. Expression of the altered
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
2-8
N-propionylated polysialic acid. The expression of
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.
To whom correspondence should be addressed. Tel.: 613-990-0821;
Fax: 613-941-1327; E-mail: harry.jennings@nrc.ca.
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