Advertisement

Bispecific Antibodies for Diagnostic Applications

  • Archana Parashar
  • Susmita Sarkar
  • Advaita Ganguly
  • Sai Kiran Sharma
  • Mavanur R. Suresh
Chapter

Abstract

Bispecific monoclonal antibodies (BsMAb) are unique engineered macromolecules that have two different pre-determined binding specificities. Their ability to simultaneously bind to a specific antigen and a given detection moiety enables them to function as excellent bifunctional immunoprobes in diagnostic assays. BsMAb are being exploited for the development of simple, rapid, and highly sensitive immunoassays for diagnosis of bacterial and viral infectious diseases. This chapter describes the use of BsMAb for the detection of Mycobacterium tuberculosis, Escherichia coli O157:H7, Bordetella pertussis, Severe Acute Respiratory Syndrome coronavirus, and Dengue virus. Further, BsMAb have been utilized for diagnosis of various types of cancers. The use of BsMAb in detection of prostate cancer and in cancer diagnostic imaging is also discussed.

Keywords

Severe Acute Respiratory Syndrome Dengue Virus Tumor Uptake Severe Acute Respiratory Syndrome Bordetella Pertussis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Armbruster DA (1993) Prostate-specific antigen: biochemistry, analytical methods, and clinical application. Clin Chem 39(2):181–195PubMedGoogle Scholar
  2. Bennett AR, MacPhee S, Betts RP (1996) The isolation and detection of Escherichia coli O157 by use of immunomagnetic separation and immunoassay procedures. Lett Appl Microbiol 22(3):237–243PubMedCrossRefGoogle Scholar
  3. Bhatnagar PK, Das D, Suresh MR (2008) Sequential affinity purification of peroxidase tagged bispecific anti-SARS-CoV antibodies on phenylboronic acid agarose. J Chromatogr B Analyt Technol Biomed Life Sci 863(2):235–241PubMedCrossRefGoogle Scholar
  4. Bopp DJ, Sauders BD, Waring AL, Ackelsberg J, Dumas N, Braun-Howland E, Dziewulski D, Wallace BJ, Kelly M, Halse T, Musser KA, Smith PF, Morse DL, Limberger RJ (2003) Detection, isolation, and molecular subtyping of Escherichia coli O157:H7 and Campylobacter jejuni associated with a large waterborne outbreak. J Clin Microbiol 41(1):174–180PubMedCrossRefGoogle Scholar
  5. Campos M, Quartin A, Mendes E, Abreu A, Gurevich S, Echarte L, Ferreira T, Cleary T, Hollender E, Ashkin D (2008) Feasibility of shortening respiratory isolation with a single sputum nucleic acid amplification test. Am J Respir Crit Care Med 178(3):300–305PubMedCrossRefGoogle Scholar
  6. Cao Y, Suresh MR (1998) Bispecific antibodies as novel bioconjugates. Bioconjug Chem 9(6):635–644PubMedCrossRefGoogle Scholar
  7. Caplan A, Kratz A (2002) Prostate-specific antigen and the early diagnosis of prostate cancer. Am J Clin Pathol 117(Suppl):S104–S108PubMedGoogle Scholar
  8. Cardillo TM, Karacay H, Goldenberg DM, Yeldell D, Chang CH, Modrak DE, Sharkey RM, Gold DV (2004) Improved targeting of pancreatic cancer: experimental studies of a new bispecific antibody, pretargeting enhancement system for immunoscintigraphy. Clin Cancer Res 10(10):3552–3561PubMedCrossRefGoogle Scholar
  9. Cattini R, Cooksey M, Robinson D, Brett G, Bacarese-Hamilton T, Jolley N (1993) Measurement of alpha-fetoprotein, carcinoembryonic antigen and prostate-specific antigen in serum and heparinised plasma by enzyme immunoassay on the fully automated serono SR1 analyzer. Eur J Clin Chem Clin Biochem 31(8):517–524PubMedGoogle Scholar
  10. CDCP (2002) Centers for Disease Control and Prevention. Pertussis 1997–2000. Morb Mortal Wkly Rep Surveill Summ 51:73–76Google Scholar
  11. Chan PK, Ng KC, Chan RC, Lam RK, Chow VC, Hui M, Wu A, Lee N, Yap FH, Cheng FW, Sung JJ, Tam JS (2004) Immunofluorescence assay for serologic diagnosis of SARS. Emerg Infect Dis 10(3):530–532PubMedCrossRefGoogle Scholar
  12. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393(6685):537–544PubMedCrossRefGoogle Scholar
  13. Das D, Suresh MR (2005) Producing bispecific and bifunctional antibodies. Methods Mol Med 109:329–346PubMedGoogle Scholar
  14. Di B, Hao W, Gao Y, Wang M, Wang YD, Qiu LW, Wen K, Zhou DH, Wu XW, Lu EJ, Liao ZY, Mei YB, Zheng BJ, Che XY (2005) Monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute-phase sera of severe acute respiratory syndrome patients. Clin Diagn Lab Immunol 12(1):135–140PubMedGoogle Scholar
  15. Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier RA, Berger A, Burguiere AM, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra JC, Muller S, Rickerts V, Sturmer M, Vieth S, Klenk HD, Osterhaus AD, Schmitz H, Doerr HW (2003) Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348(20):1967–1976PubMedCrossRefGoogle Scholar
  16. Fraser ME, Fujinaga M, Cherney MM, Melton-Celsa AR, Twiddy EM, O’Brien AD, James MN (2004) Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. J Biol Chem 279(26):27511–27517PubMedCrossRefGoogle Scholar
  17. Gold DV, Goldenberg DM, Karacay H, Rossi EA, Chang CH, Cardillo TM, McBride WJ, Sharkey RM (2008) A novel bispecific, trivalent antibody construct for targeting pancreatic carcinoma. Cancer Res 68(12):4819–4826PubMedCrossRefGoogle Scholar
  18. Goldenberg DM, Sharkey RM, Paganelli G, Barbet J, Chatal JF (2006) Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy. J Clin Oncol 24(5):823–834PubMedCrossRefGoogle Scholar
  19. Goldenberg DM, Chatal JF, Barbet J, Boerman O, Sharkey RM (2007) Cancer imaging and therapy with bispecific antibody pretargeting. Update Cancer Ther 2(1):19–31PubMedCrossRefGoogle Scholar
  20. Griffin PM, Tauxe RV (1991) The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiol Rev 13:60–98PubMedGoogle Scholar
  21. Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, Luo SW, Li PH, Zhang LJ, Guan YJ, Butt KM, Wong KL, Chan KW, Lim W, Shortridge KF, Yuen KY, Peiris JS, Poon LL (2003) Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302(5643):276–278PubMedCrossRefGoogle Scholar
  22. Gustafsson B, Lindquist U, Andersson M (1988) Production and characterization of monoclonal antibodies directed against Bordetella pertussis lipopolysaccharide. J Clin Microbiol 26(2):188–193PubMedGoogle Scholar
  23. Guttikonda S, Tang XL, Yang BM, Armstrong GD, Suresh MR (2007) Monospecific and bispecific antibodies against E. coli O157 for diagnostics. J Immunol Methods 327(1–2):1–9PubMedCrossRefGoogle Scholar
  24. Halstead SB (2007) Dengue. Lancet 370(9599):1644–1652PubMedCrossRefGoogle Scholar
  25. Hemungkorn M, Thisyakorn U, Thisyakorn C (2007) Dengue infection: a growing global health threat. Biosci Trends 1(2):90–96PubMedGoogle Scholar
  26. Hiscox JA, Cavanagh D, Britton P (1995) Quantification of individual subgenomic mRNA species during replication of the coronavirus transmissible gastroenteritis virus. Virus Res 36(2–3):119–130PubMedCrossRefGoogle Scholar
  27. Hrudey SE, Payment P, Huck PM, Gillham RW, Hrudey EJ (2003) A fatal waterborne disease epidemic in Walkerton, Ontario: comparison with other waterborne outbreaks in the developed world. Water Sci Technol 47(3):7–14PubMedGoogle Scholar
  28. Husereau DR, Suresh MR (2001) A general affinity method to purify peroxidase-tagged antibodies. J Immunol Methods 249(1–2):33–41PubMedCrossRefGoogle Scholar
  29. Jiang SS, Chen TC, Yang JY, Hsiung CA, Su IJ, Liu YL, Chen PC, Juang JL (2004) Sensitive and quantitative detection of severe acute respiratory syndrome coronavirus infection by real-time nested polymerase chain reaction. Clin Infect Dis 38(2):293–296PubMedCrossRefGoogle Scholar
  30. Josephs JE (2000) Pertussis in the adolescent and adult: a primary care concern. Clin Excell Nurse Pract 4(6):361–365PubMedGoogle Scholar
  31. Kammila S, Das D, Bhatnagar PK, Sunwoo HH, Zayas-Zamora G, King M, Suresh MR (2008) A rapid point of care immunoswab assay for SARS-CoV detection. J Virol Methods 152(1–2):77–84PubMedCrossRefGoogle Scholar
  32. Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M (2005) Growth kinetics of SARS-coronavirus in Vero E6 cells. Biochem Biophys Res Commun 329(3):1147–1151PubMedCrossRefGoogle Scholar
  33. Khosravi MJ, Papanastasiou-Diamandi A, Mistry J (1995) An ultrasensitive immunoassay for prostate-specific antigen based on conventional colorimetric detection. Clin Biochem 28(4):407–414PubMedCrossRefGoogle Scholar
  34. Klee GG, Preissner CM, Oesterling JE (1994) Development of a highly sensitive immunochemiluminometric assay for prostate-specific antigen. Urology 44(1):76–82PubMedCrossRefGoogle Scholar
  35. Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256(5517):495–497PubMedCrossRefGoogle Scholar
  36. Kreutz FT, Suresh MR (1997) Novel bispecific immunoprobe for rapid and sensitive detection of prostate-specific antigen. Clin Chem 43(4):649–656PubMedGoogle Scholar
  37. Kreutz FT, Xu DZ, Suresh MR (1998) A new method to generate quadromas by electrofusion and FACS sorting. Hybridoma 17(3):267–273PubMedCrossRefGoogle Scholar
  38. Kricka LJ (1994) Selected strategies for improving sensitivity and reliability of immunoassays. Clin Chem 40(3):347–357PubMedGoogle Scholar
  39. Lalvani A, Millington KA (2008) Screening for tuberculosis infection prior to initiation of anti-TNF therapy. Autoimmun Rev 8(2):147–152PubMedCrossRefGoogle Scholar
  40. Lau SK, Woo PC, Wong BH, Tsoi HW, Woo GK, Poon RW, Chan KH, Wei WI, Peiris JS, Yuen KY (2004) Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in sars patients by enzyme-linked immunosorbent assay. J Clin Microbiol 42(7):2884–2889PubMedCrossRefGoogle Scholar
  41. Law D (2000) Virulence factors of Escherichia coli O157 and other Shiga toxin-producing E. coli. J Appl Microbiol 88(5):729–745PubMedCrossRefGoogle Scholar
  42. Leinonen J, Lovgren T, Vornanen T, Stenman UH (1993) Double-label time-resolved immunofluorometric assay of prostate-specific antigen and of its complex with alpha 1-antichymotrypsin. Clin Chem 39(10):2098–2103PubMedGoogle Scholar
  43. Liu F, Guttikonda S, Suresh MR (2003) Bispecific monoclonal antibodies against a viral and an enzyme: utilities in ultrasensitive virus ELISA and phage display technology. J Immunol Methods 274(1–2):115–127PubMedCrossRefGoogle Scholar
  44. Madariaga MG, Jalali Z, Swindells S (2007) Clinical utility of interferon gamma assay in the diagnosis of tuberculosis. J Am Board Fam Med 20(6):540–547PubMedCrossRefGoogle Scholar
  45. Manafi M, Kremsmaier B (2001) Comparative evaluation of different chromogenic/fluorogenic media for detecting Escherichia coli O157:H7 in food. Int J Food Microbiol 71(2–3):257–262PubMedCrossRefGoogle Scholar
  46. McNicol P, Giercke SM, Gray M, Martin D, Brodeur B, Peppler MS, Williams T, Hammond G (1995) Evaluation and validation of a monoclonal immunofluorescent reagent for direct detection of Bordetella pertussis. J Clin Microbiol 33(11):2868–2871PubMedGoogle Scholar
  47. Mead PS, Slutsker L, Griffin PM, Tauxe RV (1999) Food-related illness and death in the United States reply to Dr. Hedberg. Emerg Infect Dis 5(6):841–842PubMedCrossRefGoogle Scholar
  48. Milstein C, Cuello AC (1983) Hybrid hybridomas and their use in immunohistochemistry. Nature 305(5934):537–540PubMedCrossRefGoogle Scholar
  49. NCI (2010) Key statistics about prostate cancer. http://www.cancer.org/Cancer/ProstateCancer/DetailedGuide/prostate-cancer-key-statistics. Cited on 23 July 2010
  50. Oesterling JE, Moyad MA, Wright GL Jr, Beck GR (1995) An analytical comparison of the three most commonly used prostate-specific antigen assays: Tandem-R, Tandem-E, and IMx. Urology 46(4):524–532PubMedCrossRefGoogle Scholar
  51. Palma-Nicolas JP, Bocanegra-Garcia V (2007) Innovative strategies to diagnose and monitor tuberculosis patients. Arch Bronconeumol 43(4):225–232PubMedCrossRefGoogle Scholar
  52. Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK, Yuen KY (2003) Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361(9366):1319–1325PubMedCrossRefGoogle Scholar
  53. Peltier P, Curtet C, Chatal JF, Le Doussal JM, Daniel G, Aillet G, Gruaz-Guyon A, Barbet J, Delaage M (1993) Radioimmunodetection of medullary thyroid cancer using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer. J Nucl Med 34(8):1267–1273PubMedGoogle Scholar
  54. Peppler MS (1984) Two physically and serologically distinct lipopolysaccharide profiles in strains of Bordetella pertussis and their phenotype variants. Infect Immun 43(1):224–232PubMedGoogle Scholar
  55. Poon LL, Chan KH, Wong OK, Cheung TK, Ng I, Zheng B, Seto WH, Yuen KY, Guan Y, Peiris JS (2004a) Detection of SARS coronavirus in patients with severe acute respiratory syndrome by conventional and real-time quantitative reverse transcription-PCR assays. Clin Chem 50(1):67–72PubMedCrossRefGoogle Scholar
  56. Poon LL, Guan Y, Nicholls JM, Yuen KY, Peiris JS (2004b) The aetiology, origins, and diagnosis of severe acute respiratory syndrome. Lancet Infect Dis 4(11):663–671PubMedCrossRefGoogle Scholar
  57. Rearden A, Nachtsheim DA, Frisman DM, Chiu P, Elmajian DA, Baird SM (1983) Altered cell surface antigen expression in bladder carcinoma detected by a new hemagglutinating monoclonal antibody. J Immunol 131(6):3073–3077PubMedGoogle Scholar
  58. Rearden A, Taetle R, Elmajian DA, Majda JA, Baird SM (1985) Glycophorin A on normal and leukemia cells detected by monoclonal antibodies, including a new monoclonal antibody reactive with glycophorins A and B. Mol Immunol 22(4):369–378PubMedCrossRefGoogle Scholar
  59. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Gunther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ (2003) Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300(5624):1394–1399PubMedCrossRefGoogle Scholar
  60. Schuhmacher J, Kaul S, Klivenyi G, Junkermann H, Magener A, Henze M, Doll J, Haberkorn U, Amelung F, Bastert G (2001a) Immunoscintigraphy with positron emission tomography: gallium-68 chelate imaging of breast cancer pretargeted with bispecific anti-MUC1/anti-Ga chelate antibodies. Cancer Res 61(9):3712–3717PubMedGoogle Scholar
  61. Schuhmacher J, Klivenyi G, Kaul S, Henze M, Matys R, Hauser H, Clorius J (2001b) Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET. Nucl Med Biol 28(7):821–828PubMedCrossRefGoogle Scholar
  62. Sharkey RM, Cardillo TM, Rossi EA, Chang CH, Karacay H, McBride WJ, Hansen HJ, Horak ID, Goldenberg DM (2005) Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody. Nat Med 11(11):1250–1255PubMedCrossRefGoogle Scholar
  63. Sharkey RM, Karacay H, McBride WJ, Rossi EA, Chang CH, Goldenberg DM (2007) Bispecific antibody pretargeting of radionuclides for immuno single-photon emission computed tomography and immuno positron emission tomography molecular imaging: an update. Clin Cancer Res 13(18 Pt 2):5577s–5585sPubMedCrossRefGoogle Scholar
  64. Shu PY, Huang JH (2004) Current advances in dengue diagnosis. Clin Diagn Lab Immunol 11(4):642–650PubMedGoogle Scholar
  65. Songsivilai S, Lachmann PJ (1990) Bispecific antibody: a tool for diagnosis and treatment of disease. Clin Exp Immunol 79(3):315–321PubMedCrossRefGoogle Scholar
  66. Souriau C, Hudson PJ (2003) Recombinant antibodies for cancer diagnosis and therapy. Expert Opin Biol Ther 3(2):305–318PubMedCrossRefGoogle Scholar
  67. Suresh MR (1991) Immunoassays for cancer-associated carbohydrate antigens. Semin Cancer Biol 2(6):367–377PubMedGoogle Scholar
  68. Suresh MR, Cuello AC, Milstein C (1986a) Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays. Proc Natl Acad Sci USA 83(20):7989–7993PubMedCrossRefGoogle Scholar
  69. Suresh MR, Cuello AC, Milstein C (1986b) Bispecific monoclonal antibodies from hybrid hybridomas. Methods Enzymol 121:210–228PubMedCrossRefGoogle Scholar
  70. Suresh MR, Bhatnagar PK, Das D (2008) Molecular targets for diagnostics and therapeutics of severe acute respiratory syndrome (SARS-CoV). J Pharm Pharm Sci 11(2):1s–13sPubMedGoogle Scholar
  71. Tang XL, Peppler MS, Irvin RT, Suresh MR (2004) Use of bispecific antibodies in molecular velcro assays whose specificity approaches the theoretical limit of immunodetection for Bordetella pertussis. Clin Diagn Lab Immunol 11(4):752–757PubMedGoogle Scholar
  72. Tilley PA, Kanchana MV, Knight I, Blondeau J, Antonishyn N, Deneer H (2000) Detection of Bordetella pertussis in a clinical laboratory by culture, polymerase chain reaction, and direct fluorescent antibody staining; accuracy, and cost. Diagn Microbiol Infect Dis 37(1):17–23PubMedCrossRefGoogle Scholar
  73. Vihko P, Kurkela R, Ramberg J, Pelkonen I, Vihko R (1990) Time-resolved immunofluorometric assay of human prostate-specific antigen. Clin Chem 36(1):92–95PubMedGoogle Scholar
  74. Wang LF, Shi Z, Zhang S, Field H, Daszak P, Eaton BT (2006) Review of bats and SARS. Emerg Infect Dis 12(12):1834–1840PubMedCrossRefGoogle Scholar
  75. WHO (2010) World Health Organisation online report on infectious disease. http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_AnnexA.pdf. Cited on 22 June 2010
  76. WHO-TB (2010) World Health Organisation online report on tuberculosis. http://www.who.int/mediacentre/factsheets/fs104/en/ Cited on 30 June 2010
  77. Wu HS, Chiu SC, Tseng TC, Lin SF, Lin JH, Hsu YH, Wang MC, Lin TL, Yang WZ, Ferng TL, Huang KH, Hsu LC, Lee LL, Yang JY, Chen HY, Su SP, Yang SY, Lin SY, Lin TH, Su IS (2004) Serologic and molecular biologic methods for SARS-associated coronavirus infection, Taiwan. Emerg Infect Dis 10(2):304–310PubMedGoogle Scholar
  78. Yam WC, Chan KH, Poon LL, Guan Y, Yuen KY, Seto WH, Peiris JS (2003) Evaluation of reverse transcription-PCR assays for rapid diagnosis of severe acute respiratory syndrome associated with a novel coronavirus. J Clin Microbiol 41(10):4521–4524PubMedCrossRefGoogle Scholar
  79. Yamashita M, Yamate M, Li GM, Ikuta K (2005) Susceptibility of human and rat neural cell lines to infection by SARS-coronavirus. Biochem Biophys Res Commun 334(1):79–85PubMedCrossRefGoogle Scholar
  80. Yu H, Diamandis EP (1993) Ultrasensitive time-resolved immunofluorometric assay of prostate-specific antigen in serum and preliminary clinical studies. Clin Chem 39(10):2108–2114PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Archana Parashar
    • 1
  • Susmita Sarkar
    • 1
  • Advaita Ganguly
    • 1
  • Sai Kiran Sharma
    • 1
  • Mavanur R. Suresh
    • 1
  1. 1.Faculty of Pharmacy and Pharmaceutical SciencesUniversity of AlbertaEdmontonCanada

Personalised recommendations