Evaluation of cytokine delivery systems for cancer immunotherapy

Cytokines are ideal candidates for controlled release systems; they typically have short half-lives in vivo and may be more effective with localized delivery. A novel microencapsulation technique, phase inversion nanoencapsulation (PIN), was used to encapsulate interleukin-2 or interleukin-12 in biodegradable polymer microspheres. Cytokine was quantified by ELISA and bioactivity analyzed using a murine cytotoxic T-cell line proliferation assay. The release rates of IL-2 was dependant on release buffer components; inclusion of 10% fetal calf serum resulted in significantly higher release rates compared to plain buffer. Encapsulated IL-2 remained stable at all timepoints assayed (up to 4 months) when stored at 4°C. Results indicated that PIN can be used to encapsulate IL-2 and IL-12, which were released throughout the duration of the release study (up to one month). These microsphere formulations have shown tumor suppressive affects in vivo and may provide a viable alternative to gene transfer for cancer immunotherapy.