Successful Radioimmuno-therapy for Lung Metastasis of Human Colonic Cancer in Nude Mice

Abstract

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-alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)

“…Female athymic nude mice (6 to 8 weeks old) were purchased From Taconic (Germantown, NY). Therapy studies were done using our CEACAM5+/CEACAM6+ GW-39 intrapulmonary micrometastasis model, GW-39iv (40)(41)(42). The GW-39 human colonic carcinoma has been maintained as a serially transplanted signet-ring cell cancer line since 1966 (42).…”

“…into the caudal vein of 5-to 6-week-old female nude mice. This results in f50 to 100 tumor nodules developing in the lungs and resulting in a median survival of 7 to 9 weeks (40,41). Cells were pretreated with antibody in vitro (10 Ag/mL) before implantation, and then mice were given one additional dose (100 Ag per mouse i.v.)…”

Noninternalizing Monoclonal Antibodies Are Suitable Candidates for 125I Radioimmunotherapy of Small-Volume Peritoneal Carcinomatosis

“…The long range of energetic b-particle of 90 Y and g-rays associated with 131 I are responsible for nonspecific irradiation that may cause undesirable effects such as myelosuppression. However, in mice, several studies showed that 131 I-mAbs could efficiently treat micrometastases (,1 mm) but not tumors of 2-3 mm (13,14). Other emitters, such as high-linear-energy-transfer (LET) particles, may be more attractive candidates for the therapy of solid tumors.…”

Bispecific Antibody Pretargeting of Radionuclides for Immuno–Single-Photon Emission Computed Tomography and Immuno–Positron Emission Tomography Molecular Imaging: An Update

“…To challenge the imaging ability of the pretargeting method further, we turned to a micrometastasis model of a human colonic cancer xenograft that we described earlier (80). A tumor suspension injected i.v.…”