Abstract
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 re
lease 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 granulocytemacrophage
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 colonystimulating
factor gene transduced tumor vaccines.
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