PMID: 9650561Jul 3, 1998Paper

Anti-CD3-based bispecific antibody designed for therapy of human B-cell malignancy can induce T-cell activation by antigen-dependent and antigen-independent mechanisms

International Journal of Cancer. Journal International Du Cancer
B K LinkG J Weiner

Abstract

Anti-CD3 x anti-B-cell antigen bispecific monoclonal antibodies (bsAbs) can redirect T-cell-mediated lysis toward malignant B cells. Clinical trials with CD3-based bsAbs have shown toxicity in patients which is likely related to nonspecific T-cell activation and targeting. Our current studies were designed to explore the mechanisms responsible for the observed in vivo toxicity by evaluating the immunologic effects of 2 different bsAb preparations in vitro. 1D10 was used as the tumor specific arm of the bsAbs. This antibody reacts with a variant of HLA-DR found on a majority of pre-B- and B-cell malignancies, and normal B cells in some individuals. Anti-CD3 served as the T-cell specific arm. A 1D10 x anti-CD3 bispecific IgG (bsIgG) produced using the hybrid-hybridoma method was compared to a 1D10 x anti-CD3 bispecific F(ab')2 [bsF(ab')2] produced using the leucine zipper technique. In cytotoxicity assays, both bsIgG and bsF(ab')2 induced lysis by pre-activated T cells of 1D10 (+) malignant B cells. bsIgG at high concentrations also induced lysis of 1D10 (-) tumor cells, while bsF(ab')2 did not. Proliferation of T cells induced by bsIgG and bsF(ab')2 was also evaluated. Both forms of bsAbs induced T-cell proliferation in the pres...Continue Reading

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Citations

Sep 3, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Gaurav MalviyaAlberto Signore
Jul 20, 1999·European Journal of Biochemistry·R FischerS Schillberg
Jul 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Andrew D SkoraShibin Zhou
May 14, 2005·Cancer Immunology, Immunotherapy : CII·An WillemsNico Mertens
Jan 13, 2001·Oncogene·L M Weiner, G P Adams
Sep 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rod BalhornGerry L DeNardo

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