CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. CD176 is expressed at the surface of human leukemic cells but is almost absent in normal and benign adult human tissues. Therefore, CD176 could be a promising target for antitumor immunotherapy. In the present study, pre-immunization with asialoglycophorin A (containing the CD176 oligosaccharide chains) was able to significantly improve the survival time of mice carrying CD176+ leukemia as compared to the control mice without the immunization. Furthermore, the passive transfer of CD176 antiserum which reacted only with the tumor-associated CD176 in cancer cells, was able to effectively prolong the survival time of CD176+ leukemia mice. In particular, the CD176 antiserum treatment could inhibit the growth and spreading of CD176+ leukemic cells in bone marrow, spleen, liver, and lung as evidenced by histopathological examination. CD176 antiserum could induce the apoptosis of CD176+ leukemic cells in vivo in a manner as previously observed in vitro. The data provided strong evidence that both CD176 antigen-based active immunotherapy and CD176 antibody-based passive immunotherapy lead to a therapeutic response in CD176+ leukemia mice. Therefore, both CD176 vaccine and CD176 antibody drug may be beneficial for the treatment of CD176+ leukemia patients.