Summary: Dogs with pulmonary metastasis and primary lung cancers were treated with aerosols of IL-2. Minimal toxicity was noted in 9 dogs that were treated. Two dogs with metastatic osteosarcoma had regression of pulmonary metastasis for greater than 1 year.
Publication: Khanna C, Hasz DE, Klausner JS, Katsanis, EM, and Anderson PM. Inhaled interleukin-2 liposome immunotherapy in dogs with spontaneous primary lung cancers and cancers metastatic to the lung. Cancer. 79(7): 1409-21, 1997.

Background: Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Anti-neoplastic activity of IL-2 has been modest. We have previously demonstrated the biological activity and safety of aerosols of IL-2 liposomes in normal dogs. We now report objective regression of naturally occurring pulmonary metastases in dogs after one 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 broncho-alveolar 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 immunofluoresence assay (IFA).

Results: Two of four dogs with pulmonary osteosarcoma metastases had complete regression of metastases stable for greater than 12 and greater than 20 months. One of two dogs with lung cancer had stabilization of disease for greater than 8 months; the other had progression. Toxicity was minimal. BAL cell numbers increased greater than 4 fold (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 to 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.

Conclusion: Pet dogs with naturally occurring pulmonary metastases and primary lung cancers accepted inhalation treatments easily. Non-toxic and effective treatment of pulmonary metastases of osteosarcoma is possible using nebulized IL-2 liposomes