In situ tumor vaccination with interleukin-12-encapsulated biodegradable microspheres: Induction of tumor regression and potent antitumor immunity

An alternative technology for the local and sustained delivery of cytokines to tumors for cancer immunotherapy was evaluated and shown here to induce tumor regression, suppression of metastasis, and development of systemic an titumor immunity. Treatment of tumor-bearing BALB/c mice with a single intr atumoral injection of biodegradable polylactic acid microspheres loaded wit h recombinant interleukin-12 (IL-12) promoted complete regression of the pr imary tumor and prevented the metastatic spread to the lung. Mice that expe rienced tumor regression after being treated rejected a subsequent challeng e with live tumor cells, which indicated the development of systemic antitu mor immunity. In situ tumor vaccination, i.e., injection of IL-12 microsphe res into existing tumors, was superior to vaccination of mice with mixtures of tumor cells (live or irradiated) and IL-12 microspheres in inducing sys temic antitumor immunity, The sustained release of IL-12 from the microsphe res was superior to bolus injection of free IL-12, and intratumoral deliver y of microspheres was more effective than other routes of administration. T hese studies establish the utility of biodegradable polymer microspheres as a clinically feasible alternative to systemic cytokine therapy and cytokin e gene-modified cell vaccines for the treatment of neoplastic disease.