Mediation of reduction of spontaneous and experimental pulmonary metastases by ricin A-chain immunotoxin 45-2D9-RTA with potentiation by systemic monensin in mice

• Published in: Cancer research (Chicago, Ill.) Ill.), 1988-06, Vol.48 (12), p.3496-3501
• Main Authors: ROTH, J. A, AMES, R. S, FRY, K, LEE, H. M, SCANNON, P. J
• Format: Article
• Language: English
• Subjects: Ammonium Chloride - pharmacology; Animals; Antigens, Neoplasm - analysis; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Chloroquine - pharmacology; Dimethyl Sulfoxide - pharmacology; Drug Synergism; Female; Immunotoxins - therapeutic use; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Medical sciences; Mice; Mice, Inbred BALB C; Monensin - therapeutic use; Pharmacology. Drug treatments; Ricin - therapeutic use
• ISSN: 0008-5472; 1538-7445

We developed a model to assess the therapeutic effects of the 45-2D9-ricin A-chain immunotoxin (RTA) on pulmonary metastases. The 45-2D9 mouse monoclonal antibody recognizes a Mr 74,000 glycoprotein highly expressed by rat fibroblasts transformed with the Kirsten sarcoma virus (transformed rat fibroblasts). These cells metastasize spontaneously and form lung colonies in nu/nu and irradiated BALB/c mice. Injection i.v. of 45-2D9-RTA specifically reduced formation of spontaneous pulmonary metastases and lung colonies originating from freshly disaggregated tumor cells or cultured cells. Antibody alone or mixed with unconjugated ricin A chain and an immunotoxin that recognizes a melanoma-associated antigen were ineffective. Unconjugated 45-2D9 antibody specifically blocked the 45-2D9-RTA activity in vivo. Administration of the lysosomotrophic agents ammonium chloride and chloroquine in vivo did not potentiate immunotoxin-mediated reduction in lung colonies although they were effective in vitro. Monensin potentiated 45-2D9-RTA activity in vitro and in vivo.