Abstract
Abstract In the development of monoclonal antibodies for the treatment of solid tumors, monitoring receptor occupancy (RO) on peripheral blood lymphocytes can help illustrate potential therapeutic activity occurring in the tumor environment as an assessment of pharmacodynamics (PD). There is increased interest in using these PD assessments on cells from the periphery to assess the effectiveness and efficacy of investigational therapies. In this area of therapeutic development, much focus has been placed on checkpoint inhibitors proteins/receptors such as PD-1, PD-L1, TIM3, CTLA-4, TIGIT, and multiple others. These immune checkpoint inhibitors are suitable targets since they can be upregulated and/or modulated on exhausted T cells in cancer patients. Assessing the expression of these markers in the tumor itself would be an invasive process and provide little information to correlate with pharmacokinetic results throughout the course of a clinical trial to determine optimal dose selection. However, assessment of the receptor expression and occupancy in combination with pharmacokinetics can lead to a better understanding of drug levels required to achieve optimal therapeutic performance. Monitoring the expression and binding of these molecules by drug can determine specific treatment based on the ability of the patient’s own immune system to act, while providing information to identify therapeutic responses against cancer. This poster will present an example of one such RO assessment in its development and implementation. Citation Format: Nicholas Jones, Brian Ngo, Benjamin Fancke, Jessica Limson, Floyd Davis. Use of Receptor Occupancy Assays on cells from Peripheral Blood as a Surrogate Model of the Tumor Microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4041.
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