Humanized mouse models: A valuable platform for preclinical evaluation of human cancer

Abstract

Animal models are routinely employed to assess the treatments for human cancer. However, due to significant differences in genetic backgrounds, traditional animal models are unable to meet bioresearch needs. To overcome this restriction, researchers have generated and optimized immunodeficient mice, and then engrafted human genes, cells, tissues, or organs in mice so that the responses in the model mice could provide a more reliable reference for treatments. As a bridge connecting clinical application and basic research, humanized mice are increasingly used in the preclinical evaluation of cancer treatments, particularly after gene interleukin 2 receptor gamma mutant mice were generated. Human cancer models established in humanized mice support exploration of the mechanism of cancer occurrence and provide an efficient platform for drug screening. However, it is undeniable that the further application of humanized mice still faces multiple challenges. This review summarizes the construction approaches for humanized mice and their existing limitations. We also report the latest applications of humanized mice in preclinical evaluation for the treatment of cancer and point out directions for future optimization of these models.

Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models

“…Therefore, humanized mice have recently attracted attention as an effective tool for immunotherapy evaluation [78]. Humanized mice are created by irradiating immunocompromised mice and then transplanting human CD34+ hematopoietic cells, human peripheral blood mononuclear cells, or bone marrow-liver-thymus to reproduce the human immune system [79][80][81]. Humanized mice implanted with tumor fragments derived from patients are called humanized PDX [82].…”

“…Humanized mice implanted with tumor fragments derived from patients are called humanized PDX [82]. However, humanized PDX still needs to resolve several technical issues before it can be truly effective for use in nonclinical trials due to its cost, short lifespan, unstable engraftment, and onset of graft-versus-host disease [81,83]. In addition, there are still many issues such as major histocompatibility complex incompatibility between immune cells and tumors, residual mouse innate immune cells, and lack of specific cytokines, which may cause the therapeutic response in humanized mice to be different from that of patients [81].…”