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Therapeutic Window of MuS110, a Single-Chain Antibody Construct Bispecific for Murine EpCAM and Murine CD3
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| Zeitschriftentitel: | Cancer Research |
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| Personen und Körperschaften: | , , , , , , , , , , , , , |
| In: | Cancer Research, 68, 2008, 1, S. 143-151 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>EpCAM (CD326) is one of the most frequently and highly expressed tumor-associated antigens known and recently has also been found on cancer stem cells derived from human breast, colon, prostate, and pancreas tumors. However, like many other tumor-associated antigens used for antibody-based immunotherapeutic approaches, EpCAM is expressed on normal tissues including epithelia of pancreas, colon, lung, bile ducts, and breast. To assess the therapeutic window of an EpCAM/CD3-bispecific single-chain antibody construct of the bispecific T-cell engager (BiTE) class, we constructed murine surrogate of MT110 (muS110) from single-chain antibodies specific for murine EpCAM and CD3 antigens. Immunhistochemical analysis showed that, with minor differences, the expression of EpCAM protein on a large variety of tissues from man and mouse was similar with respect to distribution and level. MuS110 exhibited significant antitumor activity at as low as 5 μg/kg in both syngeneic 4T1 orthotopic breast cancer and CT-26 lung cancer mouse models. Dosing of muS110 for several weeks up to 400 μg/kg by intraanimal dose escalation was still tolerated, indicating existence of a significant therapeutic window for an EpCAM-specific BiTE antibody in mice. MuS110 was found to have similar in vitro characteristics and in vivo antitumor activity as MT110, a human EpCAM/human CD3-bispecific BiTE antibody that currently is in formal preclinical development. [Cancer Res 2008;68(1):143–51]</jats:p> |
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| Umfang: | 143-151 |
| ISSN: |
0008-5472
1538-7445 |
| DOI: | 10.1158/0008-5472.can-07-2182 |