Intracellular domains of target antigens influence their capacity to trigger antibody-dependent cell-mediated cytotoxicity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Klaus TirochThomas Valerius

Abstract

Ab-mediated signaling in tumor cells and Ab-dependent cell-mediated cytotoxicity (ADCC) are both considered as relevant effector mechanisms for Abs in tumor therapy. To address potential interactions between these two mechanisms, we generated HER-2/neu- and CD19-derived chimeric target Ags, which were expressed in experimental tumor target cells. HER-2/neu-directed Abs were documented to mediate effective ADCC with both mononuclear cells (MNCs) and polymorphonuclear granulocytes (PMNs), whereas Abs against CD19 were effective only with MNCs and not with PMNs. We generated cDNA encoding HER-2/CD19 or CD19/HER-2 (extracellular/intracellular) chimeric fusion proteins by combining cDNA encoding extracellular domains of HER-2/neu or CD19 with intracellular domains of CD19 or HER-2/neu, respectively. After transfecting wild-type HER-2/neu or chimeric HER-2/CD19 into Raji Burkitt's lymphoma cells and wild-type CD19 or chimeric CD19/HER-2 into SK-BR-3 breast cancer cells, target cell lines were selected for high membrane expression of transfected Ags. We then investigated the efficacy of tumor cell lysis by PMNs or MNCs with CD19- or HER-2/neu-directed Ab constructs. MNCs triggered effective ADCC against target cells expressing wild-ty...Continue Reading

References

Apr 20, 1990·Cell·A Ullrich, J Schlessinger
Jun 26, 1989·Nucleic Acids Research·J Yon, M Fried
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A GhetieE S Vitetta
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·R ClynesJ V Ravetch
Oct 6, 1999·Current Opinion in Immunology·M S CraggM J Glennie
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·D M DavisJ L Strominger
Mar 31, 2000·Nature Medicine·A N Houghton, D A Scheinberg
Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Jun 3, 2000·Annual Review of Immunology·D T Fearon, M C Carroll
Aug 1, 2000·Immunology Today·M J Glennie, P W Johnson
Oct 6, 2000·Science·J V Ravetch, L L Lanier
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B StockmeyerT Valerius
Feb 13, 2001·Annual Review of Medicine·C A WhiteA J Grillo-López
Mar 13, 2001·Annual Review of Immunology·S K BromleyM L Dustin
Mar 20, 2001·Critical Reviews in Oncology/hematology·H H van Ojik, T Valerius

❮ Previous
Next ❯

Citations

Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthias PeippThomas Valerius
Oct 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefanie DererThomas Valerius
Sep 8, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marije B OverdijkPaul W H I Parren
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heike HornerBernhard Stockmeyer
Jan 1, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yvonne GuettingerBernhard Stockmeyer
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael DechantThomas Valerius
Mar 15, 2006·Journal of Immunotherapy·Karin BarbinGeorg H Fey
Sep 28, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rinpei NiwaKenya Shitara

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.

Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex, associated with a generally dismal prognosis owing to its aggressive behavior. Here are the latest discoveries pertaining to this disease.

Antibody Engineering

Antibody engineering technologies are constantly advancing to improve the clinical effectiveness of monoclonal and bispecific antibodies. Discover the latest research on Antibody Engineering here.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Stefanie DererThomas Valerius
The Journal of Immunology : Official Journal of the American Association of Immunologists
Bernhard StockmeyerMartin Herrmann
The Journal of Immunology : Official Journal of the American Association of Immunologists
Yong TangLouis M Weiner
© 2022 Meta ULC. All rights reserved