The major objective to evaluate the function of blood monocytes from children with osteosarcoma and determine their ability to be activated by liposome-encapsulated immunomodulators to lyse tumor cells. In addition, we intend to monitor this monocyte function in each individual patient from the time of diagnosis, through chemotherapy and surgery and after all treatment. This project is based on the recent observation that normal human blood monocytes can be activated by liposome-encapsulated immunomodulators to selectively lyse malignant cells in vitro. Normal cells are not lysed under similar conditions or even when co-cultivated together with tumor cells. Furthermore, multiple intravenous injection of liposome-encapsulated activators into mice with well established spontaneous lung metastases have resulted in both the activation of pulmonary macrophages and the eradication of pulmonary metastases. Osteosarcoma appears an ideal disease in which to employ liposome-encapsulated immunomodulators since its natural history parallels that of the animal model used in these in vivo liposome studies. Despite removal of the primary bone tumor and the administration of adjuvant chemotherapy, approximately 40% of children with this disease develop pulmonary metastases. Our goal is to employ activated macrophages as an adjuvant therapy to eliminate residual tumor cells in the lung and we believe that patients with osteosarcoma may benefit from the inclusion of liposome-encapsulated immunomodulators as part of their therapy. However, prior to the initiation of any such therapy, it is imperative that the monocyte function of patients with osteosarcoma be evaluated, including the effects of chemotherapy, surgery and the tumor burden. Only then can we determine if all patients are candidates for such biological therapy and when is the ideal time to commence such adjuvant therapy. For example, if chemotherapy transiently depresses monocyte function, it will be important to know the time frame of the recovery phase before proposing in vivo treatment schedules with liposome-encapsulated monocyte activators. It is expected that these experiments will lay the groundwork for designing a protocol that includes liposome-encapsulated monocyte activators as a part of the adjuvant chemotherapy treatment not only for osteosarcoma, but possible for other malignancies as well.
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