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

To target tumor cells for immunotherapy, we evaluated the feasibility of al tering the epitopes on the surface polysialic acid of tumor cells. A precur sor (N-propionylmannosamine), when incubated with leukemic cells, RBL-2H3 a nd 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 su sceptibility to cell death mediated by monoclonal antibody 13D9 (mAb 13D9), which specifically recognizes alpha2-8 N-propionylated polysialic acid. Th e expression of alpha2-8 N-propionylated polysialic acid and the lysis of t umor cells by antibody-dependent cytotoxicity depended on the time and dose of incorporation of N-propionylated mannosamine, In vivo, mAb 13D9 effecti vely controlled metastasis of leukemic cells RIMA when mice were administer ed the precursor N-propionylated mannosamine.