CD99Targeted Irinotecan Containing Nanoparticles Show Twenty-Fold Greater Anti-Tumor Effect Than Free Irinotecan For...

To assess the antitumor efficacy, pharmacokinetics, and safety of NV103, a CD99-targeted liposomal irinotecan nanoparticle, in a preclinical Ewing sarcoma model.

NV103 is a CD99-antibody targeted irinotecan containing nanoparticle, engineered to selectively deliver irinotecan to CD99 expressing tumor cells. In vitro studies measured binding, internalization, and cytotoxic IC₅₀ values in several Ewing sarcoma cell lines. In vivo, mice bearing xenografts derived from treatment-naïve and chemoresistant Ewing lines were treated. NV103 was compared with free irinotecan, untargeted nanoparticles, and Onivyde^™ at multiple dosages. Plasma pharmacokinetics of irinotecan and SN-38, biodistribution of the nanoparticles, and toxicity (body weight, organ function, and hematology) were assessed.

NV103 bound selectively to tumor cells (>80× over control), was rapidly internalized, and showed enhanced potency in vitro (IC₅₀ ≈ 3-4 nM at 0.5-1 h). In vivo, biweekly dosing at 5 mg/kg resulted in full tumor regression sustained for 140 days, even after stopping treatment at day 70. Effective suppression and survival benefit were observed at doses as low as 1 mg/kg; the ED₅₀ was estimated to be between 1-2.5 mg/kg versus 50mg/kg for free irinotecan. In a chemoresistant Ewing tumor cell line, NV103 induced similar tumor-free remission. Pharmacokinetics revealed prolonged and elevated plasma levels of irinotecan with NV103 versus free drug. No systemic toxicity was detected at doses of 10 mg/kg. Biodistribution showed tumor-preferential accumulation.

NV103 displays potent and durable antitumor activity in Ewing sarcoma at low doses with no toxicity and favorable pharmacokinetics. These findings support further development for clinical translation.