Use of Receptor Occupancy Assays on Cells from Peripheral Blood As a Model to Determine Therapeutic Efficacy

Abstract

In the development of monoclonal antibodies for the treatment of liquid or solid tumors, monitoring receptor occupancy (RO) on peripheral blood lymphocytes can help illustrate potential therapeutic activity occurring systemically, or in the tumor environment. There is increased interest in using these assessments on cells from the periphery to assess the efficacy of investigational therapies. In this area of therapeutic development, much focus has been placed on checkpoint inhibition 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 highly modulated on exhausted T cells in cancer patients. In the case of solid tumors, assessing the expression of these markers in the tumor itself via biopsy would be an invasive process that could not be performed sequentially and, therefore, would provide little information to correlate with pharmacokinetic results throughout the course of a clinical trial to determine timing and 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 a 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 receptor occupancy (RO) assessment in its development and implementation. DisclosuresNo relevant conflicts of interest to declare.