Interleukin‐2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases

• Published in: Cancer Vol. 79; no. 7; pp. 1409 - 1421
• Main Authors: Khanna, Chand, Anderson, Peter M., Hasz, Diane E., Katsanis, Emmanuel, Neville, Mary, Klausner, Jeffrey S.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.04.1997; Wiley-Liss
• Subjects: Aerosols; Animal tumors. Experimental tumors; Animals; Antineoplastic agents; Biological and medical sciences; Bronchoalveolar Lavage; Dog Diseases - drug therapy; Dogs; Drug Hypersensitivity - immunology; Experimental respiratory system tumors; General aspects; Immunity, Cellular; Immunophenotyping; inhalation; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Interleukin-2 - immunology; interleukin‐2; liposome; Liposomes; lung carcinoma; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - secondary; Lung Neoplasms - veterinary; Male; Medical sciences; Osteosarcoma - pathology; Pharmacology. Drug treatments; pulmonary metastases; Radiography; Respiratory Therapy; Time Factors; Tumors; Antineoplastic agent; Carcinoma; Toxicity; Lung; Metastasis; Bronchopulmonary; Result; Interleukin 2; Immunotherapy; Bronchus disease; Dog; Fissipedia; Lung disease; Carnivora; Immune response; Respiratory disease; Cytokine; Liposome; Malignant tumor; Inhalation; Vertebrata; Mammalia; Treatment; Animal; Aerosols; Dosage form
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/(SICI)1097-0142(19970401)79:7<1409::AID-CNCR19>3.0.CO;2-3

BACKGROUND Systemic in vivo toxicity of interleukin‐2 (IL‐2) has been problematic. Antineoplastic activity of IL‐2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL‐2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL‐2 liposome therapy. METHODS Dogs with pulmonary metastases (n = 7) and primary lung carcinoma (n = 2) were treated with aerosols of IL‐2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoalveolar lavage (BAL) and from heparinized whole blood, were assessed for cell type, immunophenotype, and tumor cytolytic activity. Immunogenicity of human IL‐2 and human serum albumin (HSA) in dogs was assessed by immunofluorescence assay. RESULTS Two of four dogs with metastatic pulmonary osteosarcoma had complete regression of metastases; the regression remained stable for more than 12 and more than 20 months, respectively. One of two dogs with lung carcinoma had stabilization of disease for more than 8 months; the other had disease progression. Toxicity was minimal. BAL cell numbers increased more than fourfold (P = 0.01) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effector lytic activity was significantly greater after 15 days of IL‐2 liposome inhalation compared with pretreatment activity (P = 0.01); however, mean BAL lytic activity decreased after 30 days and was no longer significantly greater than pretreatment BAL lytic activity. No allergic reactions were associated with inhaled IL‐2 liposome therapy. Canine antibodies against human IL‐2 and HSA were detected in all dogs. CONCLUSIONS Pet dogs with naturally occurring pulmonary metastases and primary lung carcinomas accepted inhalation treatments easily. Nontoxic and effective treatment of pulmonary metastases of osteosarcoma is possible with nebulized IL‐2 liposomes. Cancer 1997; 79:1409‐21. © 1997 American Cancer Society. Nebulized interleukin‐2 liposomes were effective and nontoxic when given to dogs with spontaneous cancers. Two of these dogs had complete regression of pulmonary metastases.