| First Author | Posekany KJ | Year | 2004 |
| Journal | Anticancer Res | Volume | 24 |
| Issue | 2B | Pages | 605-12 |
| PubMed ID | 15161001 | Mgi Jnum | J:90851 |
| Mgi Id | MGI:3044868 | Citation | Posekany KJ, et al. (2004) Suppression of Lewis lung tumor development in alpha 1,3 galactosyltransferase knock-out mice. Anticancer Res 24(2B):605-12 |
| abstractText | BACKGROUND: Humans lack the gene alpha 1,3 galactosyltransferase (GalT) and instead produce abundant cytolytic antibodies against cells bearing the antigen [gal alpha1,3 gal] (alphaGal). We have previously studied humoral anti-alphaGal responses in GalT knock-out (GalT KO) mice and shown that murine anti-alphaGal IgM, like human anti-alphaGal IgM, causes extensive complement-mediated cytolysis of GalT+ murine Lewis Lung carcinoma cells (LLCa) in vitro. Here we test the hypothesis that anti-alphaGal immune responses can inhibit the in vivo development of GalT+ tumors. MATERIALS AND METHODS: GalT KO mice orally immunized to produce anti-alphaGal antibodies (n =52) and naive non-immunized KO mice (n=37) were challenged s.c. with 10(5) LLCa tumor cells. Anti-alphaGal antibody titers were measured before and after LLCa challenge. RESULTS: Anti-alphaGal IgM titers present at challenge correlated with protection from tumor development (p<0.04). Seventy-five percent of mice with titers > or = 1:1280 remained tumor-free versus 43% of naive mice. Tumor onset was delayed in mice with circulating anti-alphaGal IgM versus naive animals (p=0.02). LLCa challenge itself induced and augmented anti-alphaGal IgM and post-challenge titers correlated highly with protection from tumor development (p<0.001). No mice with post-challenge anti-alphaGal IgM titers > or = 1:1280 developed tumors, compared to 83% of mice lacking antibody. Inhibition studies showed that 30% of post-challenge IgM recognized LLCa antigens distinct from alphaGal. Anti-alphaGal IgG was low or undetectable both pre- and post challenge and did not affect tumor formation. CONCLUSION: The finding that anti-alphaGal IgM suppresses GaIT+ tumor development in vivo supports the premise that immunotherapy using GalT expression can utilize human anti-alphaGal responses and induce significant anti-tumor effects. |
