Emerging Preclinical Applications of Humanized Mouse Models in the Discovery and Validation of Novel Immunotherapeutics and Their Mechanisms of Action for Improved Cancer Treatment

Abstract

Cancer therapeutics have undergone immense research over the past decade. While chemotherapies remain the mainstay treatments for many cancers, the advent of new molecular techniques has opened doors for more targeted modalities towards cancer cells. Although immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy in treating cancer, adverse side effects related to excessive inflammation are often reported. There is a lack of clinically relevant animal models to probe the human immune response towards ICI-based interventions. Humanized mouse models have emerged as valuable tools for pre-clinical research to evaluate the efficacy and safety of immunotherapy. This review focuses on the establishment of humanized mouse models, highlighting the challenges and recent advances in these models for targeted drug discovery and the validation of therapeutic strategies in cancer treatment. Furthermore, the potential of these models in the process of uncovering novel disease mechanisms is discussed.

Immunotherapy during the Immediate Perioperative Period: A Promising Approach against Metastatic Disease

“…Thus, an optimal design of a translational preclinical study should mimic the clinically relevant surgical setting in which immunotherapy is administered. Second, studies that utilize immune-deprived mice (to allow the transplantation of human cancer cells) should also be conducted in immune-competent mice, especially in the context of immunotherapy, possibly alongside humanized models [ 128 , 129 ]. Third, preclinical studies that assess the impact of immunotherapy during the IPP on long-term cancer outcomes should account for several aspects that may jeopardize therapy potency, including presurgical stress [ 130 ], ambient temperature [ 25 ], treatment duration and timing relative to surgery [ 99 ], and drug release platform (e.g., systemic vs. local and injection vs. suspended release) [ 131 ].…”