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MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors

Item Type:Article
Title:MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors
Creators Name:Brischwein, K. and Schlereth, B. and Guller, B. and Steiger, C. and Wolf, A. and Lutterbuese, R. and Offner, S. and Locher, M. and Urbig, T. and Raum, T. and Kleindienst, P. and Wimberger, P. and Kimmig, R. and Fichtner, I. and Kufer, P. and Hofmeister, R. and da Silva, A.J. and Baeuerle, P.A.
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 μg 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 μg 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.
Keywords:Ep-CAM, CD3, BiTE, Single-chain antibody, Xenograft model, Tumor, Animals, Mice
Source:Molecular Immunology
Publisher:Elsevier Science
Page Range:1129-1143
Date:March 2006
Official Publication:https://doi.org/10.1016/j.molimm.2005.07.034
PubMed:View item in PubMed

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