Biodegradable, timed release cytokine depots: a new approach in cancer vaccine design
Experimental studies have demonstrated that potent systemic immunity can be generated using tumor vaccines engineered by gene transfer to secrete cytokines. The physiologic principle behind these strategies involves the sustained release of high doses of cytokine local to 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. An alternate approach has been explored to generate sustained release of cytokines local to tumor cells. High doses of GM-CSF were incorporated into cell sized gelatin-chondroitin sulfate beads, which were mixed one-to-one with irradiated tumor cells prior to subcutaneous injection. This vaccination scheme resulted in systemic antitumor immune responses comparable to GM-CSF gene transduced tumor vaccines.
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