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Functional Study of a Camelid Single Domain Anti-CD22 Antibody

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Abstract

Variable antigen-binding domain of camelid single chain antibodies (VHH, Nanobody) and its conjugates are considered among very promising candidates in tumor diagnosis and treatment because of its small size, stability, and favorable bio-distribution. CD22 is a receptor that is expressed on most B cells and modulates their function. Targeting CD22 in B cell malignancies and disorders by monoclonal antibodies has shown promising results in vitro and in clinical trials. In this study, we investigate the impact of an anti-human CD22 VHH binding to CD22 on B cells and its internalization following attachment. Our findings demonstrate the proliferation inhibiting of these cells with no effect on apoptosis, in addition to the rapid internalization of the VHH.

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References

  • Arndt MA, Krauss J, Schwarzenbacher R, Vu BK, Greene S, Rybak SM (2003) Generation of a highly stable, internalizing anti-CD22 single-chain Fv fragment for targeting non-Hodgkin’s lymphoma. Int J Cancer 107:822–829

    Article  CAS  Google Scholar 

  • Behdani M, Zeinali S, Karimipour M, Khanahmad H, Schoonooghe S, Aslemarz A, Seyed N, Moazami-Godarzi R, Baniahmad F, Habibi-Anbouhi M (2013) Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth. New Biotechnol 30:205–209

    Article  CAS  Google Scholar 

  • Carnahan J, Wang P, Kendall R, Chen C, Hu S, Boone T, Juan T, Talvenheimo J, Montestruque S, Sun J (2003) Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res 9:3982s–3990s

    CAS  PubMed  Google Scholar 

  • Carnahan J, Stein R, Qu Z, Hess K, Cesano A, Hansen HJ, Goldenberg DM (2007) Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab. Mol Immunol 44:1331–1341

    Article  CAS  Google Scholar 

  • Chakravarty R, Goel S, Cai W (2014) Nanobody: the “magic bullet” for molecular imaging. Theranostics 4:386–398

    Article  CAS  Google Scholar 

  • Chaouchi N, Vazquez A, Galanaud P, Leprince C (1995) B cell antigen receptor-mediated apoptosis. Importance of accessory molecules CD19 and CD22, and of surface IgM cross-linking. J Immunol 154:3096–3104

    CAS  PubMed  Google Scholar 

  • Cyster JG, Goodnow CC (1997) Tuning antigen receptor signaling by CD22: integrating cues from antigens and the microenvironment. Immunity 6:509–517

    Article  CAS  Google Scholar 

  • Daridon C, Blassfeld D, Reiter K, Mei HE, Giesecke C, Goldenberg DM, Hansen A, Hostmann A, Frölich D, Dörner T (2010) Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthr Res Ther 12:R204

    Article  Google Scholar 

  • Doody GM, Justement LB, Delibrias CC, Matthews RJ, Lin J, Thomas ML, Fearon DT (1995) A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 269:242–244

    Article  CAS  Google Scholar 

  • Dörner T, Shock A, Goldenberg DM, Lipsky PE (2015) The mechanistic impact of CD22 engagement with epratuzumab on B cell function: implications for the treatment of systemic lupus erythematosus. Autoimmun Rev 14:1079–1086

    Article  Google Scholar 

  • Du X, Beers R, Fitzgerald DJ, Pastan I (2008) Differential cellular internalization of anti-CD19 and-CD22 immunotoxins results in different cytotoxic activity. Cancer Res 68:6300–6305

    Article  CAS  Google Scholar 

  • Fan X, Hu Y, Huang H (2014) Nanobodies: novel biomedical vehicles in targeting tumor. J Chem Pharm Res 6:458–460

    Google Scholar 

  • Faraji F, Tajik N, Behdani M, Shokrgozar MA, Zarnani AH, Shahhosseini F, Habibi-Anbouhi M (2018) Development and characterization of a camelid single domain antibody directed to human CD22 biomarker. Biotechnol Appl Biochem 65:718–725

    Article  CAS  Google Scholar 

  • Fernandes JC (2018) Therapeutic application of antibody fragments in autoimmune diseases: current state and prospects. Drug Discov Today. https://doi.org/10.1016/j.drudis.2018.06.003

    Article  PubMed  Google Scholar 

  • Gudowius S, Recker K, Laws H-J, Dirksen U, Tröger A, Wieczorek U, Furlan S, Göbel U, Hanenberg H (2006) Identification of candidate target antigens for antibody-based immunotherapy in childhood B-cell precursor ALL. Klinische Pädiatrie 218:327–333

    Article  CAS  Google Scholar 

  • Heukers R, Altintas I, Raghoenath S, de Zan E, Pepermans R, Roovers RC, Haselberg R, Hennink WE, Schiffelers RM, Kok RJ (2014) Targeting hepatocyte growth factor receptor (Met) positive tumor cells using internalizing nanobody-decorated albumin nanoparticles. Biomaterials 35:601–610

    Article  CAS  Google Scholar 

  • Homayouni V, Ganjalikhani-Hakemi M, Rezaei A, Khanahmad H, Behdani M, Lomedasht FK (2016) Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3). Iran J Basic Med Sci 19:1201

    PubMed  PubMed Central  Google Scholar 

  • Jacobi AM, Goldenberg DM, Hiepe F, Radbruch A, Burmester GR, Dörner T (2008) Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls. Ann Rheum Dis 67:450–457

    Article  CAS  Google Scholar 

  • John B, Herrin BR, Raman C, Wang Y-N, Bobbitt KR, Brody BA, Justement LB (2003) The B cell coreceptor CD22 associates with AP50, a clathrin-coated pit adapter protein, via tyrosine-dependent interaction. J Immunol 170:3534–3543

    Article  CAS  Google Scholar 

  • Keyaerts M, Xavier C, Heemskerk J, Devoogdt N, Everaert H, Ackaert C, Vanhoeij M, Duhoux FP, Gevaert T, Simon P (2016) Phase I study of 68 Ga-HER2-nanobody for PET/CT assessment of HER2 expression in breast carcinoma. J Nucl Med 57:27–33

    Article  CAS  Google Scholar 

  • Kijanka M, Dorresteijn B, Oliveira S, van Bergen en Henegouwen PM (2015) Nanobody-based cancer therapy of solid tumors. Nanomedicine 10:161–174

    Article  CAS  Google Scholar 

  • Lamb YN (2017) Inotuzumab ozogamicin: first global approval. Drugs 77:1603–1610

    Article  CAS  Google Scholar 

  • Leonard JP, Coleman M, Ketas JC, Chadburn A, Furman R, Schuster MW, Feldman EJ, Ashe M, Schuster SJ, Wegener WA (2004) Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin’s lymphoma. Clin Cancer Res 10:5327–5334

    Article  CAS  Google Scholar 

  • Mason D, Stein H, Gerdes J, Pulford K, Ralfkiaer E, Falini B, Erber W, Micklem K, Gatter K (1987) Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells. Blood 69:836–840

    Article  CAS  Google Scholar 

  • Muyldermans S (2013) Nanobodies: natural single-domain antibodies. Annu Rev Biochem 82:775–797

    Article  CAS  Google Scholar 

  • Oliveira S, Heukers R, Sornkom J, Kok RJ, En Henegouwen PMVB (2013) Targeting tumors with nanobodies for cancer imaging and therapy. J Control Release 172:607–617

    Article  CAS  Google Scholar 

  • Parish CR, Glidden MH, Quah BJ, Warren HS (2009) Use of the intracellular fluorescent dye CFSE to monitor lymphocyte migration and proliferation. Curr Protoc Immunol 84:4–9

    Article  Google Scholar 

  • Pezzutto A, Dörken B, Moldenhauer G, Clark EA (1987) Amplification of human B cell activation by a monoclonal antibody to the B cell-specific antigen CD22, Bp 130/140. J Immunol 138:98–103

    CAS  PubMed  Google Scholar 

  • Pezzutto A, Rabinovitch PS, Dörken B, Moldenhauer G, Clark EA (1988) Role of the CD22 human B cell antigen in B cell triggering by anti-immunoglobulin. J Immunol 140:1791–1795

    CAS  PubMed  Google Scholar 

  • Rezaei G, Habibi-Anbouhi M, Mahmoudi M, Azadmanesh K, Moradi-Kalbolandi S, Behdani M, Ghazizadeh L, Abolhassani M, Shokrgozar MA (2017) Development of anti-CD47 single-chain variable fragment targeted magnetic nanoparticles for treatment of human bladder cancer. Nanomedicine 12:597–613

    Article  CAS  Google Scholar 

  • Ries J, Kaplan C, Platonova E, Eghlidi H, Ewers H (2012) A simple, versatile method for GFP-based super-resolution microscopy via nanobodies. Nat Methods 9:582–584

    Article  CAS  Google Scholar 

  • Shan D, Ledbetter JA, Press OW (1998) Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood 91:1644–1652

    Article  CAS  Google Scholar 

  • Sieber T, Schoeler D, Ringel F, Pascu M, Schriever F (2003) Selective internalization of monoclonal antibodies by B-cell chronic lymphocytic leukaemia cells. Br J Haematol 121:458–461

    Article  CAS  Google Scholar 

  • Sullivan-Chang L, O’donnell RT, Tuscano JM (2013) Targeting CD22 in B-cell malignancies: current status and clinical outlook. BioDrugs 27:293–304

    Article  CAS  Google Scholar 

  • Tateno H, Li H, Schur MJ, Bovin N, Crocker PR, Wakarchuk WW, Paulson JC (2007) Distinct endocytic mechanisms of CD22 (Siglec-2) and Siglec-F reflect roles in cell signaling and innate immunity. Mol Cell Biol 27:5699–5710

    Article  CAS  Google Scholar 

  • Terstappen L, Johnsen S, Segers-Nolten I, Loken MR (1990) Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood 76:1739–1747

    Article  CAS  Google Scholar 

  • Tuscano JM, Riva A, Toscano SN, Tedder TF, Kehrl JH (1999) CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. Blood 94:1382–1392

    Article  CAS  Google Scholar 

  • Van Audenhove I, Gettemans J (2016) Nanobodies as versatile tools to understand, diagnose, visualize and treat cancer. EBioMedicine 8:40–48

    Article  Google Scholar 

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Funding

This study was supported financially by Iran University of medical sciences as a Ph.D. thesis.

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Author notes

  1. Mahdi Habibi-Anbouhi and Nader Tajik contributed equally to this work.

Authors and Affiliations

  1. Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran

    Fatemeh Faraji & Nader Tajik

  2. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Fatemeh Faraji

  3. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran

    Mahdi Habibi-Anbouhi & Mohammad Ali Shokrgozar

  4. Biotechnology Research Center, Venom & Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Tehran, Iran

    Mahdi Behdani & Fatemeh Kazemi-Lomedasht

  5. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Amir-Hassan Zarnani

Authors
  1. Fatemeh Faraji
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  2. Mahdi Habibi-Anbouhi
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  3. Mahdi Behdani
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  4. Fatemeh Kazemi-Lomedasht
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  5. Mohammad Ali Shokrgozar
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  6. Amir-Hassan Zarnani
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  7. Nader Tajik
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Correspondence to Mahdi Habibi-Anbouhi or Nader Tajik.

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Faraji, F., Habibi-Anbouhi, M., Behdani, M. et al. Functional Study of a Camelid Single Domain Anti-CD22 Antibody. Int J Pept Res Ther 26, 633–639 (2020). https://doi.org/10.1007/s10989-019-09870-y

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