The goal of cancer immune checkpoint therapies is to cure tumor-specific T cells from dysfunction which is caused by elements from tumor deposits. In this blog, we briefly describe the process of T cell exhaustion and how it can be harnessed for immuno-oncology drug discovery and more specifically to screen immune checkpoint drug candidates. First, the current function-based characterization methods for immunomodulatory drug candidates will be summarized. We have selected three methods which mimic prerequisite parameters of early T cell exhaustion (TEX). Next, we briefly describe an improved recall antigen-based potency assay as detailed elsewhere. Lastly, we describe an in vitro reversible early TEX-like model, which may be tailored with cancer-induced T cell suppression agents. Here it should be noted that cancer induced T cell dysfunction is also referred to as TEX, covering a broad spectrum of different molecular T cell pathologies. The term “T cell exhaustion” in this review mainly refers to an early stage of this process. We have devised an in vitro model that recapitulates components of tumor deposits responsible for inducing TEX.