MT95-4, a fully humanized antibody raised against aminopeptidase N, reduces tumor progression in a mouse model.
Bottom Line: To develop a novel monoclonal antibody-based cancer therapy targeting APN/CD13, we established a fully humanized anti-APN/CD13 monoclonal antibody, MT95-4.We found that expression of human APN/CD13 in murine melanoma cells increased the size of subcutaneous tumors, extent of lung metastasis and degree of angiogenesis in the subcutaneous tumors; these tumor-promoting and angiogenesis-promoting characteristics were reduced by the i.p. administration of MT95-4.These results suggested that the antitumor and anti-angiogenic effects of MT95-4 were dependent on APN/CD13 expression in tumor cells.
Affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.Show MeSH
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Mentions: To confirm the neutralizing effect of MT95-4 against APN/CD13 in vivo, we established a tail vein metastasis model and a subcutaneous xenograft model using APN-B16 cells and administered MT95-4 (1 mg/kg) i.p. twice per week in tumor-bearing mice. As shown in Figure3a and b, administration of MT95-4 reduced the number of lung surface nodules and the size of subcutaneous tumors in mice bearing APN-B16 cells. In addition, the sections of subcutaneous tumors consisting of APN-B16 cells were immunohistochemically stained with anti-CD31 antibodies, and the areas of CD31-positive vessels were significantly smaller in the MT95-4-treated group than in the control group (Fig.3c,d).
Affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.