Fig 11.

Pharmacokinetics, toxicity, and immunogenicity of JO-4. (A) Serum clearance of JO-1 and JO-4. hDSG2 transgenic mice with subcutaneous TC1-hDSG2 tumors (∼600 mm³) were intravenously injected with JO-1 or JO-4 (2 mg/kg), and serum samples were analyzed by ELISA. n = 3. Note that the y axis has a log scale. (B) Lymphocyte and platelet counts in hDSG2/TC1-hDSG2 transgenic mice after JO-1 or JO-4 injection. n = 3. (C) Therapy studies in immunocompetent hDSG2 transgenic mice with TC1-hDSG2 tumors. When tumors reached a volume of ∼80 mm³, JO-1 or JO-4 (2 mg/kg) or PBS was injected intravenously, followed 1 h later by PLD (Doxil; 1.5 mg/kg, intravenous). Treatment was repeated as indicated by arrows. Tumors were then allowed to regrow for about 2 weeks. From day 15 on, serum anti-JO-1/JO-4 antibodies were detectable by ELISA. Two more treatment cycles were performed at day 28 and day 35. JO-1 and JO-4 continued to be effective after multiple treatment cycles, even in the presence of detectable antibodies. The difference between JO-1/PLD and JO-4/PLD is significant from day 31 on. n = 10.