The immunotherapeutic effects of
interleukin-1 alpha (IL-1 alpha) encapsulated within 1-5 microns-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-1 alpha into these cells may activate them to participate in antitumor responses in vivo. Treating of
tumor-bearing mice with
IL-1 alpha 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-1 alpha-treated mice, a complete
tumor regression was observed. The timing of treatment with
IL-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha. Further studies are being aimed at increasing the immunotherapeutic efficiency of microspheric
IL-1 alpha, used as a single treatment or in combination with other treatment modalities.