Induction of long-lasting antitumor immunity by concomitant cell therapy with allogeneic lymphocytes and trifunctional bispecific antibody

Exp Hematol. 2008 Aug;36(8):997-1003. doi: 10.1016/j.exphem.2008.03.005. Epub 2008 May 20.


Objective: Use of a trifunctional bispecific antibody (trAb) given concomitantly with allogeneic cell therapy to achieve an anti tumor effect without graft-vs-host disease (GVHD).

Materials and methods: A trAb-directed against murine CD3 and human epithelial cell adhesion molecule (EpCAM) (BiLu), was given alone or concomitantly with interleukin (IL)-2-activated (LAK) H-2(b) donor splenocytes to H-2(d/b) mice inoculated with murine melanoma cells transfected with human EpCAM.

Results: A total of 32/38 mice treated with BiLu and LAK splenocytes, were tumor-free survivors without GVHD for >200 days following inoculation of a 100% lethal tumor dose (5 x 10(4)). Of 28 disease-free surviving mice previously treated with LAK splenocytes and BiLu, 24 mice proved resistance to a second tumor challenge of 10(4) cells given >210 days following the first tumor inoculation with no evidence of disease for >150 days. In contrast, only 4 of 13 disease-free survivor mice treated with naïve splenocytes and BiLu, and 5 of 10 disease-free survivor controls treated with BiLu only, resisted the second tumor challenge. Induction of antitumor immunity was more efficient and long-lasting (>150 days) in mice previously injected with a lethal tumor cell dose of 5 x 10(4) cells than in mice previously inoculated with 5 x 10(3) tumor cells.

Conclusion: Concomitantly treatment of allogeneic LAK cells and trAb-induced an efficient long-lasting antitumor immunity. Considering the documented efficacy of anti-EpCAM bispecific antibody in various metastatic cancers, clinical application of our approach may be justified in patients with minimal residual disease at high risk for tumor recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • CD3 Complex / immunology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • Cell Line, Tumor
  • Crosses, Genetic
  • Disease-Free Survival
  • Epithelial Cell Adhesion Molecule
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Immunotherapy, Adoptive*
  • Interleukin-2 / pharmacology
  • Lymphocyte Transfusion
  • Lymphocytes / immunology*
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Time Factors
  • Transgenes
  • Transplantation, Homologous


  • Antibodies, Bispecific
  • Antigens, Neoplasm
  • CD3 Complex
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Interleukin-2