In vitro antitumoral activity of baculovirus-expressed chimeric recombinant anti-CD4 antibody 13B8.2 on T-cell lymphomas

A baculovirus-expressed chimeric recombinant IgG1 (rIgG1) antibody, with Cgamma1 and Ckappa human constant domains, was derived from the murine monoclonal antibody 13B8.2, which is specific for the CDR3-like loop of the CD4 molecule. The recombinant IgG1 antibody 13B8.2 was previously shown to inhib...

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Bibliographic Details
Published in:	Journal of immunotherapy (1997) Vol. 30; no. 2; pp. 190 - 202
Main Authors:	TROADEC, Samuel, CHENTOUF, Myriam, CIRUTTI, Martine, NGUYEN, Brigitte, OLIVE, Daniel, BES, Cedric, CHARDIS, Thierry
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott 01-02-2007 Philadelphia,PA Lippincott, Williams & Wilkins
Subjects:	Animals Antibodies, Monoclonal Antibodies, Monoclonal - genetics Antibodies, Monoclonal - pharmacology Antibody-Dependent Cell Cytotoxicity Antibody-Dependent Cell Cytotoxicity - immunology Antigens, CD4 Antineoplastic agents Apoptosis Baculoviridae Baculoviridae - genetics Biological and medical sciences CD4 Antigens - immunology CD4-Positive T-Lymphocytes CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology Cell Cycle Cell Cycle - drug effects Cell Line, Tumor Cell Membrane Cell Membrane - chemistry Cell Proliferation Cell Proliferation - drug effects Complement C1q Complement C1q - immunology Endocrinology and metabolism Human health and pathology Humans Immunotherapy Life Sciences Lymphoma, T-Cell Lymphoma, T-Cell - immunology Medical sciences Mice Pharmacology. Drug treatments Receptors, IgG Receptors, IgG - immunology Antineoplastic agent T lymphoma Antibody T cell neoplasm Gene expression In vitro Virus Complementary determining region 3 CD4 baculovirus Treatment Baculoviridae Immunotherapy T-Lymphocyte Chimerism Recombinant protein CDR3-like loop Antigens Cell Line Cell Membrane Cell Proliferation Antibody-Dependent Cell Cytotoxicity Humans Antibodies IgG T-Cell Complement C1q Lymphoma Receptors Animals Cell Cycle Tumor CD4-Positive T-Lymphocytes Mice Monoclonal Apoptosis
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Summary:	A baculovirus-expressed chimeric recombinant IgG1 (rIgG1) antibody, with Cgamma1 and Ckappa human constant domains, was derived from the murine monoclonal antibody 13B8.2, which is specific for the CDR3-like loop of the CD4 molecule. The recombinant IgG1 antibody 13B8.2 was previously shown to inhibit HIV-1 replication and to abrogate the one-way mixed-lymphocyte reaction and block proliferation of CD3-stimulated peripheral blood CD4 lymphocytes from healthy donors. Before testing this recombinant anti-CD4 antibody in in vivo preclinical trials, in vitro mechanisms of action of rIgG1 13B8.2 were assessed using various CD4 T-cell lymphomas. The baculovirus-expressed rIgG1 13B8.2 antibody led to 14% to 40% proliferation inhibition of the lymphoblastic leukaemia-derived SUP-T1, the acute T lymphoma-derived CCRF-CEM and Jurkat, and the cutaneous T-Cell lymphoma-derived HUT-78 cell lines, but it did not affect the cell cycle nor induce cell apoptosis. rIgG1 antibody 13B8.2 bound the C1q fraction, leading to 9% to 17% complement-mediated lysis of the HUT-78, H9, Sup-T1, and the CCRF-CEM cell lines. No correlation was observed between cell sensitivity to rIgG1 13B8.2-triggered complement-dependent lysis and CD35-, CD46-, CD55-, and CD59-surface expression on T lymphoma cells. Using fluorescence-activated cell sorter analysis, the antibody was shown to bind to FcgammaRI/CD64-transfected IIA1.6, FcgammaRII/CD32-transfected CDw32L, and FcgammaRIII/CD16-transfected Jurkat CD16 cell lines. In correlation with these findings, rIgG1 13B8.2 induced 11% to 31% antibody-dependent cell-mediated cytotoxicity of the CCRF-CEM, SUP-T1, A2.01 CD4, and Jurkat cell lines. These convincing results on the activity of the recombinant chimeric anti-CD4 antibody 13B8.2 have led us to perform in vivo preclinical study in a murine xenograft model of CD4 lymphomas.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1524-9557 1537-4513
DOI:	10.1097/01.cji.0000211331.61019.26