In Vitro Assays for Assessing Potential Adverse Effects of Cancer Immunotherapeutics

The field of cancer immunotherapy (CIT) covers a wide and ever-growing variety of molecular platforms and modalities. Since the overall aim of CIT is to activate the immune system and elicit anticancer immune responses, a majority of adverse effects noted with CIT drugs are related to the molecule's pharmacology and exaggeration of pharmacological responses. A major challenge for CIT is that nonclinical toxicity studies utilizing healthy animals often do not identify relevant pharmacological toxicities due to low or no expression of target in nontumor tissues. Therefore, the design of a battery of in vitro assays is crucial for the assessment of potential risks to cancer patients and the set-up of an adequate safety monitoring plan for clinical trials. The effective translation of results from in vitro assays to in vivo safety assessment requires a thorough understanding of the molecule's biology and mechanism of action (MoA) and careful interpretation of desired versus exaggerated pharmacology. Given the vast array of platforms and modalities for CIT, in vitro assays to assess potential adverse effects must be tailored on an individual molecule basis. In this chapter, we highlight some of the principal types of in vitro assays conducted during the course of CIT drug development, the considerations and challenges therein, and how these assays contribute to the overall safety assessment of CIT drug candidates.