RT Journal Article
T1 Inhibition of tumor growth in vivo by in situ secretion of bispecific anti-CEA × anti-CD3 diabodies from lentivirally transduced human lymphocytes
A1 Compte, Marta
A1 Blanco, Bélen
A1 Serrano, Fernando
A1 Cuesta Martínez, Ángel
A1 Sanz, Laura
A1 Bernad, Antonio
A1 Holliger, Philipp
A1 Álvarez-Vallina, Luis
AB Infiltrating T lymphocytes are found in many malignancies, but they appear to be mostly anergic and do not attack the tumor, presumably because of defective T-cell activation events. Recently, we described a strategy for the tumor-specific polyclonal activation of tumor-resident T lymphocytes based on the in situ production of recombinant bispecific antibodies (bsAbs) by transfected nonhematological cell lines. Here, we have constructed a novel HIV-1-based lentiviral vector for efficient gene transduction into various human hematopoietic cell types. Several myelomonocytic and lymphocytic cell lines secreted the anti-carcinoembryonic antigen (CEA) × anti-CD3 diabody in a functionally active form with CD3+ T-cell lines being the most efficient secretors. Furthermore, primary human peripheral blood lymphocytes (PBLs) were also efficiently transduced and secreted high levels of functional diabody. Importantly gene-modified PBLs significantly reduced in vivo tumor growth rates in xenograft studies. These results demonstrate, for the first time, the utility of lentiviral vectors for sustained expression of recombinant bsAbs in human T lymphocytes. Such T lymphocytes, transduced ex vivo to secrete the activating diabody in autocrine fashion, may provide a promising route for a gene therapy strategy for solid human tumor
PB Springer Nature
SN 0929-1903
YR 2007
FD 2007
LK https://hdl.handle.net/20.500.14352/93869
UL https://hdl.handle.net/20.500.14352/93869
LA eng
NO Compte M, Blanco B, Serrano F, et al. Inhibition of tumor growth in vivo by in situ secretion of bispecific anti-CEA x anti-CD3 diabodies from lentivirally transduced human lymphocytes. Cancer Gene Ther. 2007;14(4):380-388. doi:10.1038/sj.cgt.7701021
NO Ministerio de Sanidad (España)
NO Comunidad Autónoma de Madrid
NO Ministerio de Educación y Ciencia (España)
DS Docta Complutense
RD 29 sept 2024