TY - JOUR
T1 - Successful radioimmuno-therapy for lung metastasis of human colonic cancer in nude mice
AU - Sharkey, Robert M.
AU - Weadock, Kevin S.
AU - Natale, Ana
AU - Haywood, Lemuel
AU - Aninipot, Rosarito
AU - Blumenthal, Rosalyn D.
AU - Goldenberg, David M.
N1 - Funding Information: Received September 21, 1990; revised February 11, 1991; accepted February 20, 1991. Supported in part by Public Health Service grant CA-39841 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Garden State Cancer Center and Center for Molecular Medicine and Immunology, Newark, NJ. We thank Dr Oscar Auerbach for reviewing the histology specimens. *Correspondence to: David M. Goldenberg, ScD, MD, Garden State Cancer Center and Center for Molecular Medicine and Immunology, 1 Bruce St, Newark, NJ 07103.
PY - 1991/5/1
Y1 - 1991/5/1
N2 - The potential for radioimmunotherapy as an adjuvant treatment for early disseminated colonic cancer was investigated in an experimental lung metastasis model. Nude mice receiving intravenous injection with a suspension of human colonic cancer cells (GW-39) developed multiple (10-100) tumor nodules throughout the lungs, and more than 50% of the animals died of extensive tumor involvement within 5- 10 weeks. Groups of eight or nine animals bearing 7-day-old tumor transplants were treated with a single intravenous injection of radioiodinated agents: either 0.15 or 0.30 mCi of whole IgG of the NP-4 murine monoclonal antibody (MAb) against carcinoembryonic antigen (CEA) or 0.15 or 0.30 mCi of whole IgG of Immu-31, an anti-α-fetoprotein (anti-AFP) MAb. Treatment of animals with 0.15 or 0.30 mCi of 131I-labeled NP-4 IgG 7 days after injection of tumor cells resulted in survival for 23 weeks after tumor implantation in four of eight and seven of nine animals, respectively. Microscopic examination revealed that over 90% of the lung tumor colonies had no evidence of surviving cells. Animals treated with 0.30 mCi of anti-AFP, an irrelevant MAb, survived 4 weeks longer than controls. Toxicity was evident in four of the 17 animals given 0.30 mCi of NP-4 IgG (specific) or anti-AFP IgG (irrelevant) MAb. These animals died within 1-3 weeks after radioantibody injection, suggesting that death was related to the radiation dose. None of the animals given 0.15 mCi of 131I-MAb died within this period. These studies suggest that radioimmunotherapy may be an important adjuvant therapy for the treatment of early metastatic cancer. Further studies are needed to confirm this finding, to ascertain whether IgG or F(ab′)2 has greater tumoricidal activity, and to determine the relevance of the conventional subcutaneous tumor xenograft model compared with this intravenous model and other tumor models. [J Natl Cancer Inst 83:627-632, 1991]
AB - The potential for radioimmunotherapy as an adjuvant treatment for early disseminated colonic cancer was investigated in an experimental lung metastasis model. Nude mice receiving intravenous injection with a suspension of human colonic cancer cells (GW-39) developed multiple (10-100) tumor nodules throughout the lungs, and more than 50% of the animals died of extensive tumor involvement within 5- 10 weeks. Groups of eight or nine animals bearing 7-day-old tumor transplants were treated with a single intravenous injection of radioiodinated agents: either 0.15 or 0.30 mCi of whole IgG of the NP-4 murine monoclonal antibody (MAb) against carcinoembryonic antigen (CEA) or 0.15 or 0.30 mCi of whole IgG of Immu-31, an anti-α-fetoprotein (anti-AFP) MAb. Treatment of animals with 0.15 or 0.30 mCi of 131I-labeled NP-4 IgG 7 days after injection of tumor cells resulted in survival for 23 weeks after tumor implantation in four of eight and seven of nine animals, respectively. Microscopic examination revealed that over 90% of the lung tumor colonies had no evidence of surviving cells. Animals treated with 0.30 mCi of anti-AFP, an irrelevant MAb, survived 4 weeks longer than controls. Toxicity was evident in four of the 17 animals given 0.30 mCi of NP-4 IgG (specific) or anti-AFP IgG (irrelevant) MAb. These animals died within 1-3 weeks after radioantibody injection, suggesting that death was related to the radiation dose. None of the animals given 0.15 mCi of 131I-MAb died within this period. These studies suggest that radioimmunotherapy may be an important adjuvant therapy for the treatment of early metastatic cancer. Further studies are needed to confirm this finding, to ascertain whether IgG or F(ab′)2 has greater tumoricidal activity, and to determine the relevance of the conventional subcutaneous tumor xenograft model compared with this intravenous model and other tumor models. [J Natl Cancer Inst 83:627-632, 1991]
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U2 - 10.1093/jnci/83.9.627
DO - 10.1093/jnci/83.9.627
M3 - Article
C2 - 1708835
SN - 0027-8874
VL - 83
SP - 627
EP - 632
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 9
ER -