ReGel polymer-based delivery of interleukin-2 as a cancer treatment.

摘要: ReGel is an aqueous, filter sterilizable ABA tri-block polymer consisting of poly-(lactide-co-glycolide) and polyethylene glycol. We tested the suitability this to provide sustained interleukin-2 (IL-2) delivery for cancer immunotherapy. ReGel/IL-2 liquid at or below room temperature, easily injectable through narrow gauge needles, but undergoes a reversible thermal transition into bioerodible depot body temperature. demonstrated that releases IL-2 over 72 96 hours in vitro, without loss bioactivity. Pharmacokinetic studies after peritumoral injection 0.1 mL mice early burst release, followed by more release kinetics (T(1/2)beta 48 h). Less than 1.5% injected dose was detectable blood kidneys during first hours. A single [1 4 million international units (MIU) ReGel/IL-2, split quadrant injections] administered bearing subcutaneous RD-995 spindle cell carcinoma. Only highest (4.0 MIU) resulted significant hypotension on day 3 injection. Weekly treatment Meth fibrosarcoma RENCA renal carcinoma with (2 MIU/dose) induced reduction tumor growth improved survival. Reduction implants remote from treated lesions also observed, suggesting systemic activation antitumor immunity. These findings establish effective system immunotherapy, while decreasing toxicity. This likely be broadly applicable other cytokines peptides.