Targeting and pharmacology of an anti-IL13Rα2 antibody and antibody-drug conjugate in a melanoma xenograft model
Parul Gupta, Ziyue Karen Jiang, Bing Yang, Lisa K. Manzuk, Edward Rosfjord, Johnny Yao, LuAnna Lemon, Kavon Noorbehesht, John David, Sujiet Puthenveetil, Jeffrey Casavant, Elwira Muszynska, Fengping Li, Mauricio Leal, Puja Sapra, Anand Giddabasappa
Abstract
competition with excess of unlabeled anti-IL13Rα2-Ab significantly reduced the tumor uptake, indicative of antigen-specific tumor accumulation. Further, FMT imaging demonstrated similar biodistribution and pharmacokinetic profiles of an auristatin-conjugated anti-IL13Rα2-ADC as compared to the parental Ab. Finally, the anti-IL13Rα2-ADC exhibited a dose-dependent anti-tumor effect on A375 xenografts, with 90% complete responders at a dose of 3 mg/kg. Taken together, both FMT and PET showed a favorable biodistribution profile for anti-IL13Rα2-Ab/ADC, along with antigen-specific tumor targeting and excellent therapeutic efficacy in the A375 xenograft model. This work shows the great potential of this anti-IL13Rα2-ADC as a targeted anti-cancer agent.