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

Abstract

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.

• Authors: Shoshana Morecki, Horst Lindhofer, Elena Yacovlev, Yael Gelfand, Peter Ruf, Shimon Slavin
• Journal: Experimental hematology (Exp Hematol) Vol. 36 Issue 8 Pg. 997-1003 (Aug 2008) ISSN: 0301-472X [Print] Netherlands
• PMID: 18495330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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