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Aptamer-based radioimmunotherapy: the feasibility and prospect in cancer therapy

  • Li Li
  • Wei Wang
  • Xiangshang Xu
  • Hui Wang
  • Shujie Liao
  • Wei Li
  • Weina Zhang
  • Dan Liu
  • Bo Cao
  • Shixuan Wang
  • Keng Shen
  • Ding Ma
Article

Abstract

Radioimmunotherapy (RIT) has emerged as an attractive and promising strategy for the management of malignant diseases. It has been proven to be quite effective in the treatment of numerous tumors, such as non-Hodgkin lymphoma, metastatic prostate cancer, melanoma, thyroid cancer, colon cancer and so on. The RIT currently used is mainly based on monoclonal antibodies to recognize target antigens. As antibodies are large molecules, this method of RIT has some limitations in in vivo use, such as the immunogenicity, the high costs and low efficiency of production. Aptamer is discovered and selected by SELEX technology. As specific recognizers and binders, aptamers and antibodies have such a close similarity as to be interchangeable to some extent. But, aptamers have many advantages over antibodies: higher affinity and specificity, smaller molecular weight, more easily synthesized and modified, more rapidly penetrating into tumors, higher tumor-to-blood distribution ratio and more easily to be cleared. In addition, since aptamer has almost no immunogenicity in vivo, it can be repeatedly administered. Thus, we believe that aptamer-based RIT will be a feasible and promising way to treat human cancers, and it might display better results in cancer treatment than antibody-based RIT. In conclusion, aptamer-based RIT is hopeful to become a key therapeutics in cancer radiotherapy in the near future.

Keywords

Radioimmunotherapy Monoclonal antibody Aptamer Radionuclide 

Notes

Acknowledgments

This work was supported by the National Key Technology R&D Program of China (2008BAI57B01), National Natural Science Foundation of China (81072132), and National Natural Science Funds for Young Scholar of China (30901586/C1701).

Conflict of interest

There is no conflict of interest among the authors in this work.

References

  1. 1.
    De Santis R, Anastasi AM, D’Alessio V, Pelliccia A, Albertoni C, Rosi A, Leoni B, Lindstedt R, Petronzelli F, Dani M, Verdoliva A, Ippolito A, Campanile N, Manfredi V, Esposito A, Cassani G, Chinol M, Paganelli G, Carminati P (2003) Novel antitenascin antibody with increased tumour localisation for Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT). Br J Cancer 88:996–1003CrossRefGoogle Scholar
  2. 2.
    Goldenberg DM, Sharkey RM (2005) Radioimmunotherapy of non-Hodgkin’s lymphoma revisited. J Nucl Med 46:383–384Google Scholar
  3. 3.
    Meredith RF, Bueschen AJ, Khazaeli MB, Plott WE, Grizzle WE, Wheeler RH, Schlom J, Russell CD, Liu T, LoBuglio AF (1994) Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49. J Nucl Med 35:1017–1022Google Scholar
  4. 4.
    Dadachova E, Nosanchuk JD, Shi L, Schweitzer AD, Frenkel A, Nosanchuk JS, Casadevall A (2004) Dead cells in melanoma tumors provide abundant antigen for targeted delivery of ionizing radiation by a mAb to melanin. Proc Natl Acad Sci USA 101:14865–14870CrossRefGoogle Scholar
  5. 5.
    Goldenberg DM, Sharkey RM, Paganelli G, Barbet J, Chatal JF (2006) Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy. J Clin Oncol 24:823–834CrossRefGoogle Scholar
  6. 6.
    Filer CN (2007) Radiolabeling of serotonergic ligands with tritium and iodine-125. J Radioanal Nucl Chem 277:707–714CrossRefGoogle Scholar
  7. 7.
    Hassan Y, Edalat R, Amir RJ, Ali BS, Simindokht SA, Azim A, Mohammad GM (2011) Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy. J Radioanal Nucl Chem 287:199–209CrossRefGoogle Scholar
  8. 8.
    Goldenberg DM, Sharkey RM (2006) Advances in cancer therapy with radiolabeled monoclonal antibodies. Q J Nucl Med Mol Imaging 50:248–264Google Scholar
  9. 9.
    Rao AV, Akabani G, Rizzieri DA (2005) Radioimmunotherapy for non-Hodgkin’s lymphoma. Clin Med Res 3:157–165CrossRefGoogle Scholar
  10. 10.
    Bartlett NL, Younes A, Carabasi MH, Forero A, Rosenblatt JD, Leonard JP, Bernstein SH, Bociek RG, Lorenz JM, Hart BW, Barton J (2008) A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood 111:1848–1854CrossRefGoogle Scholar
  11. 11.
    Bonavida B (2007) Rituximab-induced inhibition of antiapoptotic cell survival pathways: implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic and novel therapeutic interventions. Oncogene 26:3629–3636CrossRefGoogle Scholar
  12. 12.
    Byrd JC, O’Brien S, Flinn IW, Kipps TJ, Weiss M, Rai K, Lin TS, Woodworth J, Wynne D, Reid J, Molina A, Leigh B, Harris S (2007) Phase 1 study of lumiliximab with detailed pharmacokinetic and pharmacodynamic measurements in patients with relapsed or refractory chronic lymphocytic leukemia. Clin Cancer Res 13:4448–4455CrossRefGoogle Scholar
  13. 13.
    Sharkey RM, Goldenberg DM (2008) Novel radioimmunopharmaceuticals for cancer imaging and therapy. Curr Opin Investig Drugs 9:1302–1316Google Scholar
  14. 14.
    Goldsmith SJ (2010) Radioimmunotherapy of lymphoma: Bexxar and Zevalin. Semin Nucl Med 40:122–135CrossRefGoogle Scholar
  15. 15.
    Milenic DE, Brady ED, Brechbiel MW (2004) Antibody-targeted radiation cancer therapy. Nat Rev Drug Discov 3:488–499CrossRefGoogle Scholar
  16. 16.
    Deb N, Goris M, Trisler K, Fowler S, Saal J, Ning S, Becker M, Marquez C, Knox S (1996) Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody. Clin Cancer Res 2:1289–1297Google Scholar
  17. 17.
    Smith-Jones PM, Vallabahajosula S, Goldsmith SJ, Navarro V, Hunter CJ, Bastidas D, Bander NH (2000) In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen. Cancer Res 60:5237–5243Google Scholar
  18. 18.
    Wong JY, Shibata S, Williams LE, Kwok CS, Liu A, Chu DZ, Yamauchi DM, Wilczynski S, Ikle DN, Wu AM, Yazaki PJ, Shively JE, Doroshow JH, Raubitschek AA (2003) A Phase I trial of 90Y-anti-carcinoembryonic antigen chimeric T84.66 radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal cancer. Clin Cancer Res 9:5842–5852Google Scholar
  19. 19.
    Burke JM, Jurcic JG (2004) Radioimmunotherapy of leukemia. Adv Pharmacol 51:185–208CrossRefGoogle Scholar
  20. 20.
    Smith-Jones PM (2004) Radioimmunotherapy of prostate cancer. Q J Nucl Med Mol Imaging 48:297–304Google Scholar
  21. 21.
    Cheng KT (2004) 111In-Diethylenetriaminepentaacetic acid-trastuzumab. Molecular Imaging and Contrast Agent Database (MICAD)Google Scholar
  22. 22.
    Chopra A (2004) 111In-Labeled mapatumumab. Molecular Imaging and Contrast Agent Database (MICAD)Google Scholar
  23. 23.
    Leonard JP, Siegel JA, Goldsmith SJ (2003) Comparative physical and pharmacologic characteristics of iodine-131 and yttrium-90: implications for radioimmunotherapy for patients with non-Hodgkin’s lymphoma. Cancer Invest 21:241–252CrossRefGoogle Scholar
  24. 24.
    Qaim SM (2010) Radiochemical determination of nuclear data for theory and applications. J Radioanal Nucl Chem 284:489–505CrossRefGoogle Scholar
  25. 25.
    Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA Jr (1984) Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 72:77–89Google Scholar
  26. 26.
    Ferens JM, Krohn KA, Beaumier PL, Brown JP, Hellstrom I, Hellstrom KE, Carrasquillo JA, Larson SM (1984) High-level iodination of monoclonal antibody fragments for radiotherapy. J Nucl Med 25:367–370Google Scholar
  27. 27.
    Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822CrossRefGoogle Scholar
  28. 28.
    Fukusaki E, Kato T, Maeda H, Kawazoe N, Ito Y, Okazawa A, Kajiyama S, Kobayashi A (2000) DNA aptamers that bind to chitin. Bioorg Med Chem Lett 10:423–425CrossRefGoogle Scholar
  29. 29.
    Beinoraviciute-Kellner R, Lipps G, Krauss G (2005) In vitro selection of DNA binding sites for ABF1 protein from Saccharomyces cerevisiae. FEBS Lett 579:4535–4540CrossRefGoogle Scholar
  30. 30.
    Andreola ML, Pileur F, Calmels C, Ventura M, Tarrago-Litvak L, Toulme JJ, Litvak S (2001) DNA aptamers selected against the HIV-1 RNase H display in vitro antiviral activity. Biochemistry 40:10087–10094CrossRefGoogle Scholar
  31. 31.
    Jayasena SD (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45:1628–1650Google Scholar
  32. 32.
    Haes AJ, Giordano BC, Collins GE (2006) Aptamer-based detection and quantitative analysis of ricin using affinity probe capillary electrophoresis. Anal Chem 78:3758–3764CrossRefGoogle Scholar
  33. 33.
    Cho S, Lee SH, Chung WJ, Kim YK, Lee YS, Kim BG (2004) Microbead-based affinity chromatography chip using RNA aptamer modified with photocleavable linker. Electrophoresis 25:3730–3739CrossRefGoogle Scholar
  34. 34.
    Chapman JA, Beckey C (2006) Pegaptanib: a novel approach to ocular neovascularization. Ann Pharmacother 40:1322–1326CrossRefGoogle Scholar
  35. 35.
    Dougan H, Lyster DM, Vo CV, Stafford A, Weitz JI, Hobbs JB (2000) Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood. Nucl Med Biol 27:289–297CrossRefGoogle Scholar
  36. 36.
    Kusser W (2000) Chemically modified nucleic acid aptamers for in vitro selections: evolving evolution. J Biotechnol 74:27–38Google Scholar
  37. 37.
    Latham JA, Johnson R, Toole JJ (1994) The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing 5-(1-pentynyl)-2’-deoxyuridine. Nucleic Acids Res 22:2817–2822CrossRefGoogle Scholar
  38. 38.
    Collett JR, Cho EJ, Ellington AD (2005) Production and processing of aptamer microarrays. Methods 37:4–15CrossRefGoogle Scholar
  39. 39.
    Zhang P, Zhao N, Zeng Z, Feng Y, Tung CH, Chang CC, Zu Y (2009) Using an RNA aptamer probe for flow cytometry detection of CD30-expressing lymphoma cells. Lab Invest 89:1423–1432CrossRefGoogle Scholar
  40. 40.
    Girvan AC, Teng Y, Casson LK, Thomas SD, Juliger S, Ball MW, Klein JB, Pierce WM Jr, Barve SS, Bates PJ (2006) AGRO100 inhibits activation of nuclear factor-kappaB (NF-kappaB) by forming a complex with NF-kappaB essential modulator (NEMO) and nucleolin. Mol Cancer Ther 5:1790–1799CrossRefGoogle Scholar
  41. 41.
    Carrasquillo KG, Ricker JA, Rigas IK, Miller JW, Gragoudas ES, Adamis AP (2003) Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres. Invest Ophthalmol Vis Sci 44:290–299CrossRefGoogle Scholar
  42. 42.
    Chu TC, Marks JW, Lavery LA, Faulkner S, Rosenblum MG, Ellington AD, Levy M (2006) Aptamer: toxin conjugates that specifically target prostate tumor cells. Cancer Res 66:5989–5992CrossRefGoogle Scholar
  43. 43.
    Missailidis S, Perkins A (2007) Update: aptamers as novel radiopharmaceuticals: their applications and future prospects in diagnosis and therapy. Cancer Biother Radiopharm 22:453–468CrossRefGoogle Scholar
  44. 44.
    Hilger CS, Willis MC, Wolters M, Pieken WA (1999) Tc-99 m-labeling of modified RNA. Nucleosides Nucleotides 18:1479–1481CrossRefGoogle Scholar
  45. 45.
    Winnard P Jr, Chang F, Rusckowski M, Mardirossian G, Hnatowich DJ (1997) Preparation and use of NHS-MAG3 for technetium-99 m labeling of DNA. Nucl Med Biol 24:425–432Google Scholar
  46. 46.
    Hicke BJ, Stephens AW, Gould T, Chang YF, Lynott CK, Heil J, Borkowski S, Hilger CS, Cook G, Warren S, Schmidt PG (2006) Tumor targeting by an aptamer. J Nucl Med 47:668–678Google Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2011

Authors and Affiliations

  • Li Li
    • 1
  • Wei Wang
    • 1
    • 2
  • Xiangshang Xu
    • 3
  • Hui Wang
    • 1
  • Shujie Liao
    • 1
  • Wei Li
    • 1
  • Weina Zhang
    • 1
  • Dan Liu
    • 1
  • Bo Cao
    • 1
  • Shixuan Wang
    • 1
  • Keng Shen
    • 4
  • Ding Ma
    • 1
  1. 1.Cancer Biology Research Center, Tongji HospitalHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Department of Obstetrics and Gynecology, Nanfang HospitalSouthern Medical UniversityGuangzhouPeople’s Republic of China
  3. 3.Cancer Research Institute, Tongji HospitalHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  4. 4.Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical CollegeChinese Academy of Medical ScienceBeijingPeople’s Republic of China

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