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Controlled Release, Biodegradable Cytokine Depots: A New Approach in Cancer Vaccine Design¹

Departments of Oncology [P. T. G., E. M. J., H. I. L., D. M. P.], Pathology [A. L.], and Biomedical Engineering [R. A., K. L.], School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205

Experimental studies using murine tumor models have demonstrated that potent systemic immunity can be generated using tumor vaccines engineered by gene transfer to secrete certain cytokines. The underlying physiological principle behind these strategies involves the sustained release of high doses of cytokine at the site of the tumor. In some cases, this paracrine approach appears to enhance tumor antigen presentation and avoids systemic cytokine toxicity. The widespread clinical use of autologous cytokine gene transduced tumor vaccines may be limited by the technical difficulty and labor intensity of individualized gene transfer. We have therefore explored an alternate approach to generating sustained release of cytokines local to the tumor cells. High doses of granulocyte-macrophage colony-stimulating factor encapsulated in cell-sized gelatinchondroitin sulfate microspheres were mixed with irradiated tumor cells prior to s.c. injection. This vaccination scheme resulted in systemic antitumor immune responses comparable to granulocyte-macrophage colony-stimulating factor gene transduced tumor vaccines.

¹ This work is supported in part by The Cancer Research Institute (Benjamin Jacobson Family Investigator Award) and the Rothschild Foundation.

² To whom requests for reprints should be addressed, at Department of Oncology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 364, Baltimore, MD 21205.

Received 9/15/93. Accepted 11/ 2/93.

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