Improved efficacy of alpha-particle-targeted radiation therapy: dual targeting of human epidermal growth factor receptor-2 and tumor-associated glycoprotein 72

Cancer. 2010 Feb 15;116(4 Suppl):1059-66. doi: 10.1002/cncr.24793.


Background: Human epidermal growth factor receptor-2 (HER-2) and tumor-associated glycoprotein 72 (TAG-72) have proven to be excellent molecular targets for cancer imaging and therapy. Trastuzumab, which binds to HER-2, is effective in the treatment of disseminated intraperitoneal disease when labeled with (213)Bi or (212)Pb. (213)Bi-humanized CC49 monoclonal antibody (HuCC49DeltaCH2), which binds to TAG-72, inhibits the growth of subcutaneous xenografts. A next logical step to improve therapeutic benefit would be to target tumors with both molecules simultaneously.

Methods: Athymic mice bearing intraperitoneal human colon carcinoma xenografts were treated with a combination of trastuzumab and HuCC49DeltaCH2 labeled with (213)Bi administered through an intraperitoneal route. The sequence of administration also was examined.

Results: Before combining the 2 monoclonal antibodies, the effective doses of (213)Bi-CC49DeltaCH2 and (213)Bi-trastuzumab for the treatment of peritoneal disease were determined to be 500 muCi for each labeled antibody. Treatment with (213)Bi-HuCC49DeltaCH2 resulted in a median survival of 45 days and was comparable to the median survival achieved with (213)Bi-trastuzumab. Each combination provided greater therapeutic efficacy than either of the agents given alone. However, the greatest therapeutic benefit was achieved when (213)Bi-HuCC49DeltaCH2 and (213)Bi-trastuzumab were coinjected, and a median survival of 147 days was obtained.

Conclusions: Dual targeting of 2 distinct molecules in tumors such as TAG-72 and HER-2 with alpha-particle radiation resulted in an enhanced, additive, therapeutic benefit. The authors also observed that this radioimmunotherapeutic strategy was well tolerated.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alpha Particles / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Neoplasm / immunology
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / radiation effects
  • Cell Line, Tumor
  • Colonic Neoplasms / therapy*
  • Female
  • Glycoproteins / immunology*
  • Glycoproteins / radiation effects
  • Humans
  • Mice
  • Mice, Nude
  • Radioimmunotherapy / methods*
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / radiation effects
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • B72.3 antibody
  • Glycoproteins
  • tumor-associated antigen 72
  • ERBB2 protein, human
  • Receptor, ErbB-2