Therapeutic Window of MuS110, a Single-Chain Antibody Construct Bispecific for Murine EpCAM and Murine CD3
Abstract
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]
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Preclinical data from studies with muS110 demonstrated that EpCAM-specific BiTE antibodies can effectively discriminate between target antigen expressed on tumor and normal epithelial tissue.
“Preclinical data from studies with muS110, a BiTE surrogate targeting murine EpCAM and murine CD3 demonstrated that EpCAM-specific BiTE antibodies can effectively discriminate between target antigen expressed on tumor and normal epithelial tissue. 57”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [57]
The citation lists haven’t been fetched yet
References 47 · Cited by 90
- Authors
- Amann, M., Brischwein, K., Lutterbuese, P., Parr, L., Petersen, L., Lorenczewski, G., Krinner, E., Bruckmeier, S., Lippold, S., Kischel, R., Lutterbuese, R., Kufer, P., Baeuerle, P. A., & Schlereth, B.
- Affiliations
- Micromet AG, Munich, Germany and Micromet, Inc., Bethesda, Maryland
- Venue
- Cancer Research
- Published
- 2008-01-01
- Volume
- 68
- Issue
- 1
- Pages
- 143-151
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2161447915
- Cited by
- 90
- References
- 47
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 7.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- bispecific T-cell engagers, single-chain antibody, EpCAM, CD3, therapeutic window, tumor-associated antigens, anticancer activity, 4T1 breast cancer, dose escalation
- MeSH terms
- Epithelial Cell Adhesion Molecule, Animals, Antibodies, Monoclonal, Antigens, Neoplasm, Breast Neoplasms, Cytotoxicity, Immunologic, Cricetinae, Humans, Lung Neoplasms, Neoplasms, Tissue Distribution, Cell Adhesion Molecules, CD3 Complex, Antibodies, Bispecific, Mice, Single-Chain Antibodies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
