ImmunoPET helps predicting the efficacy of antibody-drug conjugates targeting TENB2 and STEAP1

摘要: The efficacy of antibody-drug conjugates (ADCs) targeted to solid tumors depends on biological processes that are hard monitor in vivo. 89Zr-immunoPET the ADC antibodies could help understand performance ADCs clinic by confirming necessary penetration, binding, and internalization. This work studied monomethyl auristatin E (MMAE) against two targets metastatic castration-resistant prostate cancer, TENB2 STEAP1, four patient-derived tumor models (LuCaP35V, LuCaP70, LuCaP77, LuCaP96.1). Three aspects biology were measured compared: was growth inhibition studies; target expression immunohistochemistry flow cytometry; antibody uptake with 111In-mAbs gamma counting or 89Zr-immunoPET. Within each model, mAb highest showed greatest potency as an ADC. Sensitivity between varied, LuCaP77 model showing weak despite high uptake. Ex vivo analysis confirmed results, a correlation expression, efficacy. We conclude data can demonstrate which candidates achieve internalization for sensitive toxic payload.