Abstract
Abstract Immunotherapeutic approaches to activate patient T cells against cancer have emerged as a promising clinical strategy for many cancer types. One critical consideration for immune activating therapies is to establish efficacious and tolerable dosing limits. The conveyed estimate of the predicted therapeutic window could be impacted by presence of circulating tumor associated antigen. Here we evaluate a Bi-specific T cell Engager (BiTE®) directed against CD3 and CDH19, a type II cadherin overexpressed >60% of melanomas. Because, to our knowledge, the shedding of CDH19 was unknown we developed an immunoassay to detect soluble CDH19 (sCDH19) in the serum of human donors and patients with metastatic melanoma. Utilizing our immunoassay to detect sCDH19, we measured elevated levels of sCDH19 in the serum of metastatic patients relative to normal donors. Additionally, the potency of this BiTE® using T-cell dependent cellular cytotoxity assays was measured. We next incorporated the range of sCDH19 amounts in patients along with BiTE® potency and present desired pharmacokinetic profiles of this therapeutic. In sum, we report that sCDH19 is present in the circulation of patients with metastatic melanoma and evaluate the impact of sCDH19 on BiTE® pharmacokinetics and human dose projections. Citation Format: Amy E. Gilbert, Ariel Avilion, David Doherty, Shyun Li, Julie Bailis, Dan Rock. Bispecific T-cell engagers: evaluation of circulating tumor-associated antigen levels and pharmacokinetics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-197.
Published Version
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