Eradication of Tumors from a Human Colon Cancer Cell Line and from Ovarian Cancer Metastases in Immunodeficient Mice by a Single-Chain Ep-CAM-/CD3-Bispecific Antibody Construct
Abstract
Bispecific T-cell engager (BiTE) are a class of bispecific single-chain antibodies that can very effectively redirect cytotoxic T cells for killing of tumor target cells. Here, we have assessed the in vivo efficacy of one representative, called bscEp-CAMxCD3, with specificity for tumors overexpressing epithelial cell adhesion molecule (Ep-CAM) in human xenograft models. Cells of the human colon carcinoma line SW480 were mixed at a 1:1 ratio with unstimulated human peripheral mononuclear cells, s.c. injected in nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mice, and animals were treated with bscEp-CAMxCD3. Five daily i.v. injections of as little as 100 ng per mouse of bscEp-CAMxCD3 completely prevented tumor outgrowth when treatment was started at the day of tumor cell inoculation. BscEp-CAMxCD3 was also efficacious when administered up to 8 days after xenograft injection. Established tumors could be eradicated in all animals by five 10 μg doses given between days 8 and 12 after tumor cell inoculation. To test the efficacy of bscEp-CAMxCD3 in a more physiologic model, pieces of primary metastatic tumor tissue from ovarian cancer patients were implanted in NOD/SCID mice. Partial tumor engraftment and growth was observed with four of six patient samples. Treatment of established tumors with daily 5 μg doses led to a significant reduction and, in some cases, eradication of human tumor tissue. These effects obviously relied on the tumor-resident T cells reactivated by bscEp-CAMxCD3. Our data show that the class of single-chain bispecific antibodies has very high antitumor efficacy in vivo and can use previously unstimulated T cells at low effector-to-target ratios.
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Since MT110 does not activate murine T cells, tumor resident human T cells, being tolerized or anergized, could be reactivated and were present in sufficient number to eliminate the xenograft.
“Since MT110 does not activate murine T cells, this result suggests that tumor resident human T cells, being tolerized or anergized, could be reactivated, and were present in sufficient number to eliminate the xenograft. 56”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [56]
MT110 was active against human ovarian metastatic tissues grafted in immunodeficient mice in the absence of human peripheral mononuclear cells.
“MT110 was also active against human ovarian metastatic tissues grafted in immunodeficient mice in the absence of human peripheral mononuclear cells.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [56]
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- Authors
- Schlereth, B., Fichtner, I., Lorenczewski, G., Kleindienst, P., Brischwein, K., da Silva, A., Kufer, P., Lutterbuese, R., Junghahn, I., Kasimir-Bauer, S., Wimberger, P., Kimmig, R., & Baeuerle, P. A.
- Affiliations
- 1Micromet AG, Munich, Germany;
- 2Experimental Pharmacology and Oncology, Berlin-Buch, Berlin, Germany; and
- 3Department of Gynecology and Obstetrics, University of Essen, Essen, Germany
- University of Duisburg-Essen (DE)
- Venue
- Cancer Research
- Published
- 2005-04-01
- Volume
- 65
- Issue
- 7
- Pages
- 2882-2889
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2096996532
- Cited by
- 132
- References
- 29
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 8 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 10
- FWCI
- 7.13
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Keywords
- bispecific T-cell engagers, EpCAM, CD3, colon cancer, xenografts, tumor eradication, tumor-infiltrating T cells, T cell redirection, NOD/SCID mice, SW480 cells
- MeSH terms
- Epithelial Cell Adhesion Molecule, Animals, Antibody Specificity, Antigens, Neoplasm, Colonic Neoplasms, Female, Humans, Mice, Inbred C57BL, Ovarian Neoplasms, Peritoneal Neoplasms, Cell Adhesion Molecules, Mice, SCID, Mice, Inbred NOD, CD3 Complex, Antibodies, Bispecific, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice
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