MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors
Abstract
We have developed a novel single-chain Ep-CAM-/CD3-bispecific single-chain antibody construct designated MT110. MT110 redirected unstimulated human peripheral T cells to induce the specific lysis of every Ep-CAM-expressing tumor cell line tested. MT110 induced a costimulation independent polyclonal activation of CD4- and CD8-positive T cells as seen by de novo expression of CD69 and CD25, and secretion of interferon gamma, tumor necrosis factor alpha, and interleukins 2, 4 and 10. CD8-positive T cells made the major contribution to redirected tumor cell lysis by MT110. With a delay, CD4-positive cells could also contribute presumably as consequence of a dramatic upregulation of granzyme B expression. MT110 was highly efficacious in a NOD/SCID mouse model with subcutaneously growing SW480 human colon cancer cells. Five daily doses of 1 microg MT110 on days 0-4 completely prevented tumor outgrowth in all mice treated. The bispecific antibody construct also led to a durable eradication of established tumors in all mice treated with 1 microg doses of MT110 on days 8-12 after tumor inoculation. Finally, MT110 could eradicate patient-derived metastatic ovarian cancer tissue growing under the skin of NOD/SCID mice. MT110 appears as an attractive bispecific antibody candidate for treatment of human Ep-CAM-overexpressing carcinomas.
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In vitro characterizations of MT110 recapitulated the results obtained with MT103 on tumor cell lines, demonstrating the generality of the BiTE format.
“In vitro characterizations of MT110 have recapitulated the results obtained with MT103 on tumor cell lines, thereby demonstrating the generality of the BiTE format. 55”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [55]
In NOD/SCID mice, as little as 100 ng of MT110 can prevent tumor outgrowth after injection of a 1:1 ratio of human colon carcinoma cells mixed with unstimulated human peripheral mononuclear cells.
“A study in NOD/SCID mice demonstrated that as little as 100 ng of MT110 can prevent tumor outgrowth after an injection of a 1:1 ratio of human colon carcinoma cells mixed with unstimulated human peripheral mononuclear cells.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [55]
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- Authors
- Brischwein, K., Schlereth, B., Guller, B., Steiger, C., Wolf, A., Lutterbuese, R., Offner, S., Locher, M., Urbig, T., Raum, T., Kleindienst, P., Wimberger, P., Kimmig, R., Fichtner, I., Kufer, P., Hofmeister, R., da Silva, A. J., & Baeuerle, P. A.
- Affiliations
- University of Duisburg-Essen (DE)
- Corresponding author
- Baeuerle, Patrick A.
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 43
- Issue
- 8
- Pages
- 1129-1143
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W1993325062
- Cited by
- 256
- References
- 64
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 14 · 2022: 17 · 2021: 18 · 2020: 14 · 2019: 13 · 2018: 10 · 2017: 18 · 2016: 11 · 2015: 22 · 2014: 15 · 2013: 11 · 2012: 16
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Immunology (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 single-chain antibody, EpCAM, CD3, T cell redirection, adoptive T cell therapy, CD8+ T cells, CD4+ T cells, granzyme B, tumor cell lysis, colon cancer, metastatic ovarian cancer, NOD/SCID mouse model, tumor eradication, interferon-gamma, CD69, CD25
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibody Specificity, Cytotoxicity, Immunologic, Disease Models, Animal, Dose-Response Relationship, Drug, Humans, Kinetics, Lymphocyte Activation, Neoplasms, Recombinant Proteins, CD4-Positive T-Lymphocytes, Mice, SCID, Mice, Inbred NOD, CD3 Complex, Antibodies, Bispecific, CD8-Positive T-Lymphocytes, Antigens, CD19, Cell Line, Tumor, Mice, Single-Chain Antibodies
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