The Use of the Humanized Mouse Model in Gene Therapy and Immunotherapy for HIV and Cancer

Abstract

HIV and cancer remain prevailing sources of morbidity and mortality worldwide. There are current efforts to discover novel therapeutic strategies for the treatment or cure of these diseases. Humanized mouse models provide the investigative tool to study the interaction between HIV or cancer and the human immune system in vivo. These humanized models consist of immunodeficient mice transplanted with human cells, tissues, or hematopoietic stem cells that result in reconstitution with a nearly full human immune system. In this review, we discuss preclinical studies evaluating therapeutic approaches in stem cell-based gene therapy and T cell-based immunotherapies for HIV and cancer using a humanized mouse model and some recent advances in using checkpoint inhibitors to improve antiviral or antitumor responses.

A comparative study of cartilage engineered constructs in immunocompromised, humanized and immunocompetent mice

“…Nevertheless, current humanized mice lack secondary lymphoid tissue and can only partially mimic the complexity of a fully developed, human immune system, which is the coordinated response of stromal, lymphoid, myeloid and secondary lymphoid structures. Furthermore, the remaining murine immune system prevents the complete human engraftment and murine cytokines do not fully support human myeloid and lymphoid development [20,21]. While effort are currently undergoing to overcome these limitations, it is still an open question whether humanized mice could be used in the tissue engineering field and represent a useful model in the preclinical study of tissueengineered graft transplantation.…”

Lessons Learned From Failures and Success Stories of HIV Breakthroughs: Are We Getting Closer to an HIV Cure?

“…The usage of humanized mice model has been an essential contribution to the investigation of HIV biology, including life cycle, immunobiology, drug or vaccine target/delivery, tissue reservoir and persistency/latency (Policicchio et al, 2016;Marsden and Zack, 2017;Masse-Ranson et al, 2018). Even though the model is able to 'mimic' human cells present in peripheral blood or tissue, and exhibit both innate and adaptive response toward HIV infection, there are still some limitations (Nixon et al, 2017;Carrillo et al, 2018). The size and biology of the animal, which affects the blood volume for viral load, peripheral blood cells for functional assay, and the short lifespan are some of the issues to consider.…”

Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives

“…There are multiple humanized mouse models available, which are briefly summarized in Table 3 and more extensively reviewed elsewhere [87]. Generally, to create these models immunodeficient mice are injected with human cells, tissues, or stem cells that reconstitute in these animals a human immune system [88]. The development of any humanized mouse is complex, time consuming, and expensive compared to xenograft models, but they provide a unique environment to test OAd replication in human tumors and the ability to study human immune responses in vivo [73].…”