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DTIC ADA470864: Breast Cancer Therapy Using Antibody-Endostatin Fus... |
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by Defense Technical Information Center |
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To produce a more effective form of trastuzumab and |
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improve efficacy of endostatin we constructed several |
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anti- HER2 IgG3-endostatin fusion proteins by fusing |
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human endostatin to the 3 end of a humanized anti-HER2 |
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IgG3 antibody. Antibody targeting is designed to enhance |
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local delivery of endostatin to tumor as well as increase |
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endostatin half-life. We constructed two endostatin |
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fusion proteins based on native human endostatin and/or a |
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mutant endostatin with a P125A substitution to confer |
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increased antiangiogenic activity. Native and P125A |
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mutant fusion proteins inhibited tube formation and |
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proliferation of HUVEC in vitro although P125A fusion |
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protein showed greater inhibition than either native |
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endostatin or endostatin fusion protein. Treatment of |
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established SKBR-3 with the mutant P125A fusion resulted |
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in complete regression of xenografts in SCID mice (5/5 |
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tumor free) compared to untreated anti-HER2 lgG3 human |
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endostatin or the native endostatin fusion protein |
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treated mice. Combination of huEndo fusion protein and |
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Avastin synergistically enhanced anti-tumor activity. |
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Linking endostatin to an antibody may significantly |
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enhance anti-tumor activity of trastuzumab. Mutant P125A |
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fusion antibody showed better anti-tumor activity. |
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Targeting antiangiogenic proteins using antibody is a |
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versatile approach that could be applied to other targets |
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(e.g. EGFR PSMA) or using other antiangiogenic protein |
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domains. |
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Date Published: 2018-06-13 23:38:35 |
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Identifier: DTIC_ADA470864 |
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Item Size: 11873539 |
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Language: english |
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Media Type: texts |
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# Topics |
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DTIC Archive; Shin, Seung-Uon; MIAMI ... |
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@chris85 |
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