Biochemical engineering of surface alpha 2-8 polysialic acid for immunotargeting tumor cells.
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.
Liu
T
T
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada.
Guo
Z
Z
Yang
Q
Q
Sad
S
S
Jennings
H J
HJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000939:Epitopes / Q000276:immunology; D005260:Female; D006595:Hexosamines / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D012794:Sialic Acids / Q000096:biosynthesis / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006595:Hexosamines; C415828:N-propionylmannosamine; D012794:Sialic Acids; C415847:alpha(2-8)-N-propionylpolysialic acid; C071290:alpha(2-8)polysialic acid