PURPOSE: The high molecular weight melanoma-associated antigen (HMW-MAA) is an 
attractive target for immunotherapy of malignant melanoma. We have recently 
generated a vaccine based on the HMW-MAA mimotope 225D9.2+ that was able to 
induce anti-HMW-MAA antibodies with antitumor activity in vitro. Here, we 
investigated the antitumor activity of these antibodies in a human melanoma 
xenotransplant severe combined immunodeficient (SCID) mouse model.
EXPERIMENTAL DESIGN: Tumors were established by injecting the human melanoma 
518A2 cells into C.B.17 SCID/SCID mice. In tumor prevention experiments, 200 
microg purified total IgG antibodies were injected intravenously the same day or 
on day 5 in therapeutic experiments. Antibody administration was repeated every 
fourth day and tumor volumes were measured. Antibody specificity and tumor 
infiltration by macrophages were investigated by immunohistochemistry.
RESULTS: Within 35 days after cell inoculation, antibody treatment reduced tumor 
growth up to 40% in the therapeutic and up to 62% in the tumor prevention 
experiments compared with the control mice. In tumors of all groups, a similar 
distribution of the HMW-MAA and no differences in infiltration of macrophages 
were detected by immunohistochemistry.
CONCLUSIONS: Here, we showed that antibodies induced by the 225D9.2+ mimotope 
effectively inhibited melanoma tumor growth. Additional mechanisms besides 
antibody-dependent cell cytotoxicity like disruption of interactions of melanoma 
cells mediated by extracellular matrix components seem to be involved in tumor 
growth inhibition. Based on our findings, we suggest that active immunization 
with this mimotope might be a promising strategy for treatment of melanoma.