USE OF A BISPECIFIC ANTI-CD3xCD19 ANTIBODY FOR TARGETING OF CD3+CD56+ HUMAN CYTOTOXIC CELLS AGAINST CD19+ LEUKEMIA AND LYMPHOMA CELLS

P. Lefterova, A. Märten, P. Buttgereit, S. Weineck, B. Micka, C. Scheffold, D. Huhn, I.G.H. Schmidt-Wolf

Rheinische Friedrich-Wilhelms-Universität, Bonn; Virchow-Klinikum, Humboldt-Universität, Berlin, Germany and Bone Marrow Transplantation Program, Stanford University Medical Center, Stanford, CA.

ABSTRACT :

Highly efficient NK-like T immunologic effector cells termed cytokine-induced killer (CIK) cells have been described. These cells are able to purge hematopoietic progenitor cells contaminated with lymphoma cells and exert limited toxicity to stem cells. Most interestingly, CIK cells have been shown to eradicate established human lymphoma cells in a SCID mouse xenograft model in vivo. Here, our study was aimed at increasing the cytotoxic activity of CIK cells using the bispecific antibody anti-CD3xCD19. Binding of anti-CD3xCD19 bispecific antibody to CIK cell cultures derived from peripheral blood was demonstrated using flow cytometry. Binding of the antibody to CIK cells was immediate in most cases. For the target side, several B cell lines were found to express CD19 on the cell surface. There was an impressive increase in sensitivity to CIK-mediated lysis of various cells by preincubation of the targets with the bispecific antibody against CD3xCD19 as shown in a 51Cr release assay. The addition of anti-CD3xCD19 to CIK cells preincubated with an anti-CD28 antibody did not lead to a further increase in cytotoxic activity. Interestingly, preincubation of Daudi and "380" cells with an anti-CD3 monoclonal antibody led to further increase of cytotoxic sensitivity as compared to addition of the bispecific CD3xCD19 antibody alone. In conclusion, our data suggest that the cytotoxic activity of CD3+CD56+ immunologic effector cells can be further increased by the use of a bispecific antibody anti-CD3xCD19.