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MT95-4, a fully humanized antibody raised against aminopeptidase N, reduces tumor progression in a mouse model.

Akita S, Hattori N, Masuda T, Horimasu Y, Nakashima T, Iwamoto H, Fujitaka K, Miyake M, Kohno N - Cancer Sci. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

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Effects of MT95-4 on tumor progression in the tail vein metastasis model and subcutaneous tumor model using APN-B16 cells. Mice were administered MT95-4 or control IgG (1 mg/kg) i.p. twice a week. (a) Evaluation of the number of lung surface nodules in the tail vein metastasis model following injection of APN-B16 cells. The number of tumor nodules on the lung surface was counted 21 days after injection of APN-B16 cells. Each bar represents the mean number of nodules from eight mice per group. $P < 0.05. (b) Evaluation of tumor volume in a subcutaneous tumor model using APN-B16 cells. The sizes of subcutaneous tumors were measured twice a week for 2 weeks after inoculation of APN-B16 cells. The data represent the means (± SEM) from eight mice per group. $P < 0.05. (c) Evaluation of angiogenesis in subcutaneous tumors derived from APN-B16 cells. The area of CD31-positive vessels was measured. Data represent the means (± SEM) from eight mice per group. $$$P < 0.01. (d) Immunohistochemical staining for CD31 in a subcutaneous tumor. Scale bar, 100 μm.
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fig03: Effects of MT95-4 on tumor progression in the tail vein metastasis model and subcutaneous tumor model using APN-B16 cells. Mice were administered MT95-4 or control IgG (1 mg/kg) i.p. twice a week. (a) Evaluation of the number of lung surface nodules in the tail vein metastasis model following injection of APN-B16 cells. The number of tumor nodules on the lung surface was counted 21 days after injection of APN-B16 cells. Each bar represents the mean number of nodules from eight mice per group. $P < 0.05. (b) Evaluation of tumor volume in a subcutaneous tumor model using APN-B16 cells. The sizes of subcutaneous tumors were measured twice a week for 2 weeks after inoculation of APN-B16 cells. The data represent the means (± SEM) from eight mice per group. $P < 0.05. (c) Evaluation of angiogenesis in subcutaneous tumors derived from APN-B16 cells. The area of CD31-positive vessels was measured. Data represent the means (± SEM) from eight mice per group. $$$P < 0.01. (d) Immunohistochemical staining for CD31 in a subcutaneous tumor. Scale bar, 100 μm.

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).


MT95-4, a fully humanized antibody raised against aminopeptidase N, reduces tumor progression in a mouse model.

Akita S, Hattori N, Masuda T, Horimasu Y, Nakashima T, Iwamoto H, Fujitaka K, Miyake M, Kohno N - Cancer Sci. (2015)

Effects of MT95-4 on tumor progression in the tail vein metastasis model and subcutaneous tumor model using APN-B16 cells. Mice were administered MT95-4 or control IgG (1 mg/kg) i.p. twice a week. (a) Evaluation of the number of lung surface nodules in the tail vein metastasis model following injection of APN-B16 cells. The number of tumor nodules on the lung surface was counted 21 days after injection of APN-B16 cells. Each bar represents the mean number of nodules from eight mice per group. $P < 0.05. (b) Evaluation of tumor volume in a subcutaneous tumor model using APN-B16 cells. The sizes of subcutaneous tumors were measured twice a week for 2 weeks after inoculation of APN-B16 cells. The data represent the means (± SEM) from eight mice per group. $P < 0.05. (c) Evaluation of angiogenesis in subcutaneous tumors derived from APN-B16 cells. The area of CD31-positive vessels was measured. Data represent the means (± SEM) from eight mice per group. $$$P < 0.01. (d) Immunohistochemical staining for CD31 in a subcutaneous tumor. Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520645&req=5

fig03: Effects of MT95-4 on tumor progression in the tail vein metastasis model and subcutaneous tumor model using APN-B16 cells. Mice were administered MT95-4 or control IgG (1 mg/kg) i.p. twice a week. (a) Evaluation of the number of lung surface nodules in the tail vein metastasis model following injection of APN-B16 cells. The number of tumor nodules on the lung surface was counted 21 days after injection of APN-B16 cells. Each bar represents the mean number of nodules from eight mice per group. $P < 0.05. (b) Evaluation of tumor volume in a subcutaneous tumor model using APN-B16 cells. The sizes of subcutaneous tumors were measured twice a week for 2 weeks after inoculation of APN-B16 cells. The data represent the means (± SEM) from eight mice per group. $P < 0.05. (c) Evaluation of angiogenesis in subcutaneous tumors derived from APN-B16 cells. The area of CD31-positive vessels was measured. Data represent the means (± SEM) from eight mice per group. $$$P < 0.01. (d) Immunohistochemical staining for CD31 in a subcutaneous tumor. Scale bar, 100 μm.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Show MeSH
Related in: MedlinePlus