Biochemical engineering of surface alpha 2-8 polysialic acid for immunotargeting tumor cells.

Abstract

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 alpha2-8 polysialic acid with N-propionyl groups. Expression of the altered alpha2-8 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 alpha2-8 N-propionylated polysialic acid. The expression of alpha2-8 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.

• Authors: T Liu, Z Guo, Q Yang, S Sad, H J Jennings
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 42 Pg. 32832-6 (Oct 20 2000) ISSN: 0021-9258 [Print] United States
• PMID: 10976100 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Epitopes
• Hexosamines
• N-propionylmannosamine
• Sialic Acids
• alpha(2-8)-N-propionylpolysialic acid
• alpha(2-8)polysialic acid

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antibody-Dependent Cell Cytotoxicity
• Epitopes (immunology)
• Female
• Hexosamines (metabolism)
• Immunotherapy (methods)
• Kinetics
• Leukemia, Basophilic, Acute
• Leukemia, Experimental (immunology, therapy)
• Mice
• Mice, Inbred C57BL
• Rats
• Sialic Acids (biosynthesis, immunology)
• Tumor Cells, Cultured