Skip to main content

Advertisement

Log in

Immunogenicity of Iodine 131 chimeric tumor necrosis therapy monoclonal antibody in advanced lung cancer patients

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Purpose

Iodine-131 radiolabeled chimeric tumor necrosis therapy monoclonal antibody (131I-TNT) has been approved for the treatment of advanced lung cancer in China. In the present study, the immunogenicity of TNT was studied in advanced lung cancer patients using BIACORE and enzyme linked immunosorbent assay (ELISA) methods.

Experimental design

Serum samples from 78 advanced lung cancer patients were analyzed for antibody development to TNT after systemic or intratumoral administration of two doses of 131I-TNT. Patients’ sera were obtained before, and 2 weeks and 2 months after 131I-TNT radioimmunotherapy.

Results

Four of 78 lung cancer patients (4/78 or 5.13%) developed antibodies to TNT as measured by ELISA method, and 7 of 78 patients (8.97%) development anti-TNT antibody as measured by BIACORE biosensor after 2 doses of 131I-TNT administration (P > 0.05). All the 4 ELISA-positive patients were also BIACORE-positive. Among the 7 BIACORE-positive patients, 5 (of 42, 11.9%) patients receiving intravenous TNT injection developed antibodies to TNT, and 2 (of 36, 5.56%) patients, receiving intratumoral therapy developed antibodies to TNT. The route of administration of the radiolabeled TNT antibody was not a statistically significant factor in the incidence of anti-TNT antibody. Detailed BIACORE serological analysis showed that the induced antibodies were mostly of the IgG1 subclass.

Conclusions

131I-TNT was immunogenic in only a small minority of advanced lung cancer patients (8.97%). The route of administration did not statistically influence the incidence of anti-TNT antibody after TNT radioimmunotherapy in lung cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wagner HN, Wiseman GA, Marcus CS, Nabi HA, Nagle CE, Fink-Bennett DM, Lamonica DM, Conti PS (2002) Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-labeled anti-CD20 monoclonal antibody. J Nucl Med 43:267–272

    PubMed  CAS  Google Scholar 

  2. Ross JS, Schenkein DP, Pietrusko R, Rolfe M, Linette GP, Stec J, Stagliano NE, Ginsburg GS, Symmans WF, Pusztai L, Hortobagyi GN (2004) Targeted therapies for cancer 2004. Am J Clin Pathol 122:598–609

    Article  PubMed  CAS  Google Scholar 

  3. Vose JM (2004) Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin’s lymphoma. Oncologist 9:160–172

    Article  PubMed  CAS  Google Scholar 

  4. Mirick GR, Bradt BM, Denardo SJ, Denardo GL (2004) A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words. Q J Nucl Med Mol Imaging 48:251–257

    PubMed  CAS  Google Scholar 

  5. Reff ME, Heard C (2001) A review of modifications to recombinant antibodies: attempt to increase efficacy in oncology applications. Crit Rev Oncol Hematol 40:25–35

    Article  PubMed  CAS  Google Scholar 

  6. Epstein AL, Chen FM, Taylor CR (1988) A novel method for the detection of necrotic lesions in human cancers. Cancer Res 48:5842–5848

    PubMed  CAS  Google Scholar 

  7. Chen FM, Taylor CR, Epstein AL (1989) Tumor necrosis treatment of ME-180 human cervical carcinoma model with 131I-labeled TNT-1 monoclonal antibody. Cancer Res 49:4578–4585

    PubMed  CAS  Google Scholar 

  8. Chen FM, Epstein AL., Li Z, Taylor CR (1990) A comparative autoradiographic study demonstrating differential intra-tumor localization of monoclonal antibodies to cell surface (Lym-1) and intracellular (TNT-1) antigens. J Nucl Med 31:1059–1066

    PubMed  CAS  Google Scholar 

  9. Epstein AL, Khawli LA, Chen F-M, Hu P, Glasky MS, Taylor CR (1995) Tumor necrosis imaging and treatment of solid tumors. In: Torchillin VP (ed) Handbook of targeted delivery of imaging agents. CRC, Boca Raton, pp 259–288

    Google Scholar 

  10. Hornick JL, Sharifi J, Khawli LA, Hu P, Biela BH, Mizokami MM, Yun A, Taylor CR, Epstein AL (1998) chTNT-3/B, a new chemically modified chimeric monoclonal antibody directed against DNA for the tumor necrosis treatment of solid tumors. Cancer Biother Radiopharm 13:255–268

    Article  PubMed  CAS  Google Scholar 

  11. Epstein AL, Chen D, Ansari A et al (1991) Radioimmunodetection of necrotic lesions in human tumors using I-131 labeled TNT-1 F(ab’)2 monoclonal antibody. Antibody Immunoconjugates Radiopharm 4:151–161

    Google Scholar 

  12. Chen S, Yu L, Jiang C, Zhao Y, Sun D, Li S, Liao G, Chen Y, Fu Q, Tao Q, Ye D, Hu P, Khawli LA, Taylor CR, Epstein AL, Ju DW (2005) Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J Clin Oncol 23:1538–1547

    Article  PubMed  Google Scholar 

  13. Patel SJ, Shapiro WR, Laske DW, Jensen RL, Asher AL, Wessels BW, Carpenter SP, Shan JS (2005) Safety and feasibility of convection-enhanced delivery of Cotara for the treatment of malignant glioma: initial experience in 51 patients. Neurosurgery 56:1243–1252

    Article  PubMed  Google Scholar 

  14. Street HH, Goris ML, Fisher GA, Wessels BW, Cho C, Hernandez C, Zhu HJ, Zhang Y, Nangiana JS, Shan JS, Roberts K, Knox SJ (2006) Phase I study of 131I-chimeric (ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer. Cancer Biother Radiopharm 21:243–256

    Article  PubMed  CAS  Google Scholar 

  15. Yu L, Chen T, Li Z, Xu C, Jiang C, Hu P, Khawli L, Taylor CR, Epstein AL (2006) 131I-chTNT-3 radioimmunotherapy of 43 patients with advanced lung cancer. Cancer Biother Radiopharm 21:5–14

    Article  PubMed  Google Scholar 

  16. Chen FM, Wisner JR Jr, Omachi H, Renner IG, Taylor CR, Epstein AL (1990) Localization of monoclonal antibody TNT-1 in experimental kidney infarction of the mouse. FASEB J 4:3033–3039

    PubMed  CAS  Google Scholar 

  17. Anderson PM, Wiseman GA, Lewis BD, Charboneau JW, Dunn WL, Carpenter S, Chew T (2003) A phase I safety and imaging study using radiofrequency ablation (RFA) followed by 131I-chTNT-1/B radioimmunotherapy adjuvant treatment of hepatic metastases. Cancer Therapy 1:297–306

    Google Scholar 

  18. Granzow R (1994) Biomolecular interaction anlysis. Methods 6:93–205

    Article  Google Scholar 

  19. Carter P (2001) Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 1:118–129

    Article  PubMed  CAS  Google Scholar 

  20. Goldenberg DM (2002) Targeted therapy of cancer with radiolabeled antibodies. J Nucl Med 43:693–713

    PubMed  CAS  Google Scholar 

  21. Milenic DE (2002) Monoclonal antibody-based therapy strategies: providing options for the cancer patient. Curr Pharm Des 8:1749–1764

    Article  PubMed  CAS  Google Scholar 

  22. Ross JS, Gray K, Gray GS, Worland PJ, Rolfe M (2003) Anticancer antibodies. Am J Clin Pathol 119:472–485

    Article  PubMed  CAS  Google Scholar 

  23. Azinovic I, DeNardo GL, Lamborn KR, Mirick G, Goldstein D, Bradt BM, DeNardo SJ (2006) Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies. Cancer Immunol Immunother 55:1451–1418

    Article  PubMed  CAS  Google Scholar 

  24. Pimm MV (1994) Possible consequences of human antibody responses on the biodistribution of fragments of human, humanized or chimeric monoclonal antibodies: a note of caution. Life Sci 55:PL45–49

    Article  PubMed  CAS  Google Scholar 

  25. HAMA Survey Group (1993) Survey of methods for measuring human anti-mouse antibodies. Clin Chim Acta 215:153–163

    Article  Google Scholar 

  26. Khazaeli MB, Conry M, LoBuglio AF (1994) Human immune response to monoclonal antibodies. J Immunother 15:42–52

    Article  CAS  Google Scholar 

  27. Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC, Norton L (1996) Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 14:737–744

    PubMed  CAS  Google Scholar 

  28. Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA, Slamon DJ (1998) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16:2659–2671

    PubMed  CAS  Google Scholar 

  29. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17:2639–2648

    PubMed  CAS  Google Scholar 

  30. Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D (2001) Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19:843–850

    PubMed  CAS  Google Scholar 

  31. DeNardo GL, Mirick GR, Kroger LA, Bradt BM, Lamborn KR, DeNardo SJ (2003) Characterization of human IgG anti-mouse antibody (HAMA) in patients with B-cell malignancies. Clin Cancer Res 9:4013s–4021s

    PubMed  CAS  Google Scholar 

  32. Ritter G, Cohen LS, Williams C Jr, Richards EC, Old LJ, Welt S (2001) Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33. Cancer Res 61:6851–6859

    PubMed  CAS  Google Scholar 

  33. Welt S, Ritter G, Williams C Jr, Cohen LS, John M, Jungbluth A, Richards EA, Old LJ, Kemeny NE (2003) Phase I study of anticolon cancer humanized antibody A33. Clin Cancer Res 9:1338–1346

    PubMed  CAS  Google Scholar 

  34. Kure M, Katsura Y, Kosano H, Noritake M, Watanabe T, Iwaki Y, Nishigori H, Matsuoka T (2005) A trial to assess the amount of insulin antibodies in diabetic patients by surface plasmon resonance. Intern Med 44:100–106

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

These studies were supported by funds provided by Medipharm Biotech Co, Shanghai, China, Shanghai Pudong Science & Technology Bureau, and Science and Technology Commission of Shanghai Municipality. We thank Mr. Wan Yunfang, Ms. Qiu Ling, and Ms. Qu Chunjie for their careful monitoring of the TNT clinical trial in lung cancer patients; professor Zhang Jing at Department of Statistics, Tongji University for her excellent work in Statistics.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dianwen Ju.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, H., Cao, C., Li, B. et al. Immunogenicity of Iodine 131 chimeric tumor necrosis therapy monoclonal antibody in advanced lung cancer patients. Cancer Immunol Immunother 57, 677–684 (2008). https://doi.org/10.1007/s00262-007-0406-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-007-0406-0

Keywords

Navigation