Characterization and Use of Neuraminidase-modified L1210 Plasma Membranes for Protection against Tumor Growth1

Purified plasma membranes were prepared from L1210 as ertes tumor cells and analyzed for their protein and carbohy drate composition. Conditions were developed for treating the isolated plasma membranes with Vibrio cholerae neuraminidase (VCN) so that 88% of the N-acetylneuraminic acid was removed without changing membrane proteins or other mem brane carbohydrate constituents. The VCN-induced modifica tions were characterized by labeling VCN-treated and un treated L1210 cells by the galactose oxidase:sodium [3H]borohydride procedure. This showed that /V-acetylneuraminic acid is the predominant saccharide at the nonreducing terminus of plasma membrane glycoproteins and that galactose and/or A/-acetylgalactosamine residues are penultimate to these. VCN modification exposed the penultimate residues and was not limited to any single plasma membrane glycoprotein. DBA/2J mice were given i.p. injections of VCN-treated or untreated membranes and were challenged 3 weeks later with 10" viable L1210 cells. Mice pretreated with VCN-treated membranes resisted the tumor challenge; those receiving untreated mem branes or no treatment succumbed to the tumor. Our results demonstrate that appropriately modified plasma membranes can be used to induce resistance to tumor growth. They also suggest that tumor cell membrane carbohydrate structures have an important role in this phenomenon.