INTERLEUKIN-2 LIPOSOME INHALATION-THERAPY IS SAFE AND EFFECTIVE FOR DOGS WITH SPONTANEOUS PULMONARY METASTASES

BACKGROUND. Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Antineoplastic activity of IL-2 has been modest. The aut hors have previously demonstrated the biologic activity and safety of aerosols of IL-2 liposomes in normal dogs. They now report objective r egression 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 wi th aerosols of IL-2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoal veolar lavage (BAL) and from heparinized whole blood, were assessed fo r cell type, immunophenotype, and tumor cytolytic activity. Immunogeni city 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 reg ression remained stable for more than 12 and more than 20 months, resp ectively. One of two dogs with lung carcinoma had stabilization of dis ease for more than 8 months; the other had disease progression. Toxici ty was minimal. BAL cell numbers increased more than fourfold (P = 0.0 1) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effecto r lytic activity was significantly greater after 15 days of IL-2 lipos ome inhalation compared with pretreatment activity (P = 0.01); however , mean BAL lytic activity decreased after 30 days and was no longer si gnificantly greater than pretreatment BAL lytic activity, No allergic reactions were associated with inhaled IL-2 liposome therapy. Canine a ntibodies against human IL-2 and HSA were detected in all dogs. CONCLU SIONS. Pet dogs with naturally occurring pulmonary metastases and prim ary lung carcinomas accepted inhalation treatments easily. Nontoxic an d effective treatment of pulmonary metastases of osteosarcoma is possi ble with nebulized IL-2 liposomes. (C) 1997 American Cancer Society.