Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity

High-dose chemotherapy (HDC) with autologous bone marrow or peripheral stem cell transplantation is discussed as one option to treat the extensive sta ge of a variety of tumors. Effective methods to eliminate contaminating tum or cells from human bone marrow or stem cell grafts may improve the outcome of the patients. We investigated 3 recombinant bispecific single-chain ant ibodies (bscAbs) directed against 17-1A (EpCAM), c-erbB-2 (HER-2/neu) and L eY on the one and CD3 on the other binding site for their ability to induce lysis of epithelial tumor cells by retargeting autochthonous T lymphocytes present in bone marrow mononuclear cells (BMMC) and in peripheral stem cel l mononuclear cells (PSMC), The bscAbs showed remarkable specific lysis of different epithelial tumor cell lines with BMMCs as well as with PSMCs as e ffector cells. Investigation of the alpha 17-1A-alpha CD3 bscAb revealed a significant correlation between the percentage of CD3(+) cells present in t he BMMCs and the rate of lysis as well as the absence of detrimental effect s on the viability of hematopoietic progenitor cells as determined by colon y-forming unit assays (CFUs). Our results indicate that recombinant bispeci fic single-chain antibodies could be new tools for purging of human bone ma rrow and peripheral stem cell grafts from contaminating epithelial cancer c ells for patients receiving autologous stem cell transplantation after HDC. (C) 2001 Wiley-Liss, Inc.