IgA as therapeutic antibody.

This review is focused on the promises of IgA as a new therapeutic antibody. For more than 30 years IgG molecules have been used in the clinic in the fields of oncology, hematology, auto immune diseases and infections. However, IgA might be a good alternative, since it recruits different effector cells, i.e. polymorphonuclear cells or neutrophils, but can also activate monocytes and macrophages. The present knowledge, but also future direction for IgA- based drugs are discussed.

[1]  C. Arteaga,et al.  Optimal targeting of HER2-PI3K signaling in breast cancer: mechanistic insights and clinical implications. , 2013, Cancer research.

[2]  A. Houghton,et al.  Fc receptors are required in passive and active immunity to melanoma. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Kinet,et al.  Structure of the Fc fragment of human IgE bound to its high-affinity receptor FcεRIα , 2000, Nature.

[4]  M. Daha,et al.  Clearance kinetics and tissue distribution of aggregated human serum IgA in rats. , 1989, Immunology.

[5]  P. Wallace,et al.  Bispecific molecules directed to the Fc receptor for IgA (Fc alpha RI, CD89) and tumor antigens efficiently promote cell-mediated cytotoxicity of tumor targets in whole blood. , 1998, Journal of immunology.

[6]  W. Gong,et al.  Phenotypic and functional change of cytokine‐activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses , 2001, Journal of leukocyte biology.

[7]  C. Klein,et al.  Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. , 2013, Blood.

[8]  F. Geissmann,et al.  A Subset of Human Dendritic Cells Expresses IgA Fc Receptor (CD89), Which Mediates Internalization and Activation Upon Cross-Linking by IgA Complexes , 2001, The Journal of Immunology.

[9]  L. Fiette,et al.  Neutrophils mediate antibody-induced antitumor effects in mice. , 2013, Blood.

[10]  J. Lund,et al.  FcαRI (CD89) as a Novel Trigger Molecule for Bispecific Antibody Therapy , 1997 .

[11]  A. Zuercher,et al.  Reversal of Arthritis by Human Monomeric IgA Through the Receptor‐Mediated SH2 Domain–Containing Phosphatase 1 Inhibitory Pathway , 2015, Arthritis & rheumatology.

[12]  J. V. D. van de Winkel,et al.  Structure and function of human IgA Fc receptors (Fc alpha R). , 1996, Critical reviews in immunology.

[13]  P. Parren,et al.  IgA EGFR antibodies mediate tumour killing in vivo , 2013, EMBO molecular medicine.

[14]  R. Bende,et al.  CD20 deficiency in humans results in impaired T cell-independent antibody responses. , 2010, The Journal of clinical investigation.

[15]  P. Parren,et al.  The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden , 2011, Haematologica.

[16]  Sherie L. Morrison,et al.  The N-Glycans Determine the Differential Blood Clearance and Hepatic Uptake of Human Immunoglobulin (Ig)a1 and Iga2 Isotypes , 2000, The Journal of experimental medicine.

[17]  P. Wallace,et al.  Differential Effect of Cytokine Treatment on Fcα Receptor I- and Fcγ Receptor I-Mediated Tumor Cytotoxicity by Monocyte-Derived Macrophages , 2000, The Journal of Immunology.

[18]  S. Lohse,et al.  Serum-free production and purification of chimeric IgA antibodies. , 2009, Journal of immunological methods.

[19]  Marjolein van Egmond,et al.  FcαRI-positive liver Kupffer cells: Reappraisal of the function of immunoglobulin A in immunity , 2000, Nature Medicine.

[20]  P. Bjorkman,et al.  Insights into IgA-mediated immune responses from the crystal structures of human FcαRI and its complex with IgA1-Fc , 2003, Nature.

[21]  J. Jansen,et al.  Both activating and inhibitory Fc gamma receptors mediate rituximab-induced trogocytosis of CD20 in mice. , 2012, Immunology letters.

[22]  E. van Garderen,et al.  IgA and the IgA Fc receptor. , 2001, Trends in immunology.

[23]  R. Zinkernagel,et al.  A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. , 2000, Science.

[24]  R. Monteiro,et al.  IgA Fc receptors. , 2003, Annual review of immunology.

[25]  Sheng Yao,et al.  Advances in targeting cell surface signalling molecules for immune modulation , 2013, Nature Reviews Drug Discovery.

[26]  K. Tarte,et al.  Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells , 2012, Haematologica.

[27]  M. van Egmond,et al.  Immunoglobulin A , 2011, mAbs.

[28]  P. Sondermann,et al.  Purification, crystallization and X-ray diffraction analysis of the extracellular part of the human Fc receptor for IgA, Fc α RI (CD89) , 2003 .

[29]  I. Moura,et al.  Identification of FcαRI as an Inhibitory Receptor that Controls Inflammation: Dual Role of FcRγ ITAM , 2005 .

[30]  M. Hulett,et al.  Identification of residues in the first domain of human Fc alpha receptor essential for interaction with IgA. , 1999, Journal of immunology.

[31]  C. Anderson,et al.  The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Leusen,et al.  Mac-1 (CD11b/CD18) as Accessory Molecule for FcαR (CD89) Binding of IgA1 , 2002, The Journal of Immunology.

[33]  J. Leusen,et al.  Mechanisms of action of CD20 antibodies. , 2012, American journal of cancer research.

[34]  Michael E. Williams,et al.  The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes1 , 2006, The Journal of Immunology.

[35]  P. Parren,et al.  In vivo cytotoxicity of type I CD20 antibodies critically depends on Fc receptor ITAM signaling. , 2010, Cancer research.