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

Mol Immunol. 2006 Mar;43(8):1129-43. doi: 10.1016/j.molimm.2005.07.034. Epub 2005 Sep 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology*
  • Antibodies, Bispecific / therapeutic use*
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody Specificity
  • Antigens, CD19 / metabolism
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Kinetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Recombinant Proteins / isolation & purification
  • Single-Chain Antibodies


  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Antigens, CD19
  • CD3 Complex
  • MT110 monoclonal antibody
  • Recombinant Proteins
  • Single-Chain Antibodies