Cancer Immunotherapies and Humanized Mouse Drug Testing Platforms

Abstract

Cancer immunotherapy is a type of treatment that restores and stimulates human immune system to inhibit cancer growth or eradicate cancer. It serves as one of the latest systemic therapies, which has been approved to treat different types of cancer in patients. Nevertheless, the clinical response rate is unsatisfactory and the response observed is mostly a partial response in patients. Despite the continuous improvement and identification of novel cancer immunotherapy, there is a pressing need to establish a robust platform to evaluate the efficacy and safety of pre-clinical drugs, simulate the interaction between patients’ tumor and immune system, and predict patients’ responses to the treatment. In this review, we summarize the pros and cons of existing immuno-oncology assay platforms, especially the humanized mouse models for the screening of cancer immunotherapy drugs. In addition, various emerging trends and progress of utilizing humanized mouse models as the screening tool are discussed. Of note, humanized mouse models can also be used for further development of personalized precision medicines to treat cancer. Collectively, these highlight the significance of humanized mouse models as the important platform for the screening of next generation cancer immunotherapy in vivo .

Patient-Derived Xenograft Models in Urological Malignancies: Urothelial Cell Carcinoma and Renal Cell Carcinoma

“…Blinova et al used humanized NSG mice to test PDL-1 blocker durvalumab and demonstrated PDL-1 expression in PDX models with significant stagnation of tumor growth [73]. It is hoped that further development of humanized mouse PDX models will allow for the study of the interaction of the tumor and the human immune system, as early models suggest that both therapeutic outcomes and side effects can be recapitulated [82].…”

A novel rabbit derived anti-HER2 antibody with pronounced therapeutic effectiveness on HER2-positive breast cancer cells in vitro and in humanized tumor mice (HTM)

“…Worth to mention is that due to their human like characteristics HTM are becoming increasingly important in the field of preclinical treatment studies. The value of mice with a human immune system to evaluate treatment success, failure and side effects involved has been recently highlighted by the US Food and Drug Administration [31,32]. Importantly, in TM (i.e., in the absence of human immune cells) the B100 treatment efficiency was not nearly as high as in HTM (i.e., in the presence of human immune cells).…”

Humanized Mice as an Effective Evaluation System for Peptide Vaccines and Immune Checkpoint Inhibitors

“…The immunization with vaccines may reveal not only the effect of a specific vaccine, but it may also provide information regarding the patient immune response to mimic the anticancer/pathogen response. The current status of the humanized mouse system involving next generation humanized mice and its limitations is shown in Figure 1 (cellular immunity) and discussed below [95,96]. emerged as a distinctive side effect of ipilimumab and occasionally of nivolumab [92].…”

“…The current status of the humanized mouse system involving next generation humanized mice and its limitations is shown in Figure 1 (cellular immunity) and discussed below. [95,96]…”

“…Among them, Ashizawa et al reported that class I and class II MHC KO NOG mice (NOG dKO) transplanted with human PBMC and tumor cell lines showed higher anticancer effects after PD-1 antibody treatment [135]. In these mouse strains, transplanted tumor cells and immune cells can be engrafted, and the anticancer effect of human immune cells can be observed (reviewed by Chen et al [95]). The mouse system had an advantage, which is that the restriction of HLA type could be avoided by using PBMC, which contain the same patient's T cells and antigen-presenting cells.…”