Local Delivery of IL-1α Polymeric Microspheres for the Immunotherapy of an Experimental Fibrosarcoma

Abstract

The immunotherapeutic effects of interleukin-1α (IL-1α) encapsulated within 1–5 μm-diameter poly (D, L-lactide) microspheres and delivered intratumorally into fibrosarcoma-bearing mice were investigated. Such microspheres are avidly taken up by macrophages, and directing IL-1α into these cells may activate them to participate in antitumor responses in vivo. Treating of tumor-bearing mice with IL-1α microspheres has increased their survival rate, as compared with control mice, untreated or treated with microspheres containing bovine serum albumin (BSA). In 20% of the IL-1α-treated mice, a complete tumor regression was observed. The timing of treatment with IL-1α microspheres was crucial; optimal survival and regression rates were observed in mice treated 24 hr postinjection of the tumor cells. Administration of three doses of IL-1α microspheres on days 1, 8, and 15 postinjection of tumor cells resulted in longer survival rates. Histopathology studies on regressed tumors revealed extensive areas of tumor cell degeneration and necrotic tissue surrounded by a large number of inflammatory cells. A similar picture was observed when IL-1α microspheres were administered into the footpad of control mice, whereas the tissue reaction to BSA microspheres was much milder. Thus, it appears that tumor regression is mainly due to the antitumor effects of IL-1α. Further studies are being aimed at increasing the immunotherapeutic efficiency of microspheric IL-1α, used as a single treatment or in combination with other treatment modalities.

• Biodegradable microspheres
• IL-1α
• Macrophage activation
• Tumor immunotherapy