Human Immune System Mice With Autologous Tumor for Modeling Cancer Immunotherapies

Sun, Liguang; Jin, Chunhui; Tan, Shulian; Liu, Wentao; Yang, Yong‐Guang

doi:10.3389/fimmu.2020.591669

Cited by 6 publications

(8 citation statements)

References 66 publications

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“…In addition, the generation of HLA-restricted tumour antigen-specific T cells is challenging owing to the HLA mismatch and lack of a human thymic epithelium that supports T cell development. Autograft tumour models (Table 3) have several advantages that would potentially enable the generation of HLA-restricted, tumour antigen-specific T cell responses and would reproduce the phenotype and therapeutic response in patients more faithfully than allograft models 61,62,120,[236][237][238][239] . An autograft Hu-SRC model would require the presence of HLA class I and II molecules for optimal T cell development and function.…”

Section: Future Directionsmentioning

confidence: 99%

Humanized mouse models for immuno-oncology research

et al. 2023

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Immunotherapy has emerged as a promising treatment paradigm for many malignancies and is transforming the drug development landscape. Although immunotherapeutic agents have demonstrated clinical efficacy, they are associated with variable clinical responses, and substantial gaps remain in our understanding of their mechanisms of action and specific biomarkers of response. Currently, the number of preclinical models that faithfully recapitulate interactions between the human immune system and tumours and enable evaluation of human-specific immunotherapies in vivo is limited. Humanized mice, a term that refers to immunodeficient mice co-engrafted with human tumours and immune components, provide several advantages for immuno-oncology research. In this Review, we discuss the benefits and challenges of the currently available humanized mice, including specific interactions between engrafted human tumours and immune components, the development and survival of human innate immune populations in these mice, and approaches to study mice engrafted with matched patient tumours and immune cells. We highlight the latest advances in the generation of humanized mouse models, with the aim of providing a guide for their application to immuno-oncology studies with potential for clinical translation.• Next-generation humanized mouse models are being generated to better recapitulate the development of human innate and adaptive immunity. The development and use of novel humanized mouse platforms will accelerate the discovery and testing of new immunotherapies for patients with cancer.Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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Section: Future Directionsmentioning

confidence: 99%

Humanized mouse models for immuno-oncology research

et al. 2023

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“…that reflected the patient-specific immunity and cancer pathological characteristics was pointed out. 20 In addition to the aforementioned function like testing the efficacy of new CAR-T cells, the Hu-HSC disease model can be used to characterize the generation and function of cytokine lineage, mem-…”

Section: Meritmentioning

confidence: 99%

“…With the continuous promotion of CAR‐T application to clinical practice, research on the recurrence and adverse reactions of many patients after treatment has also been carried out. In a research project specifically focused on HIS, a strategy to construct personalized Hu‐HSC mice that reflected the patient‐specific immunity and cancer pathological characteristics was pointed out 20 …”

Section: Hu‐hsc Modelmentioning

confidence: 99%

Progress, implications, and challenges in using humanized immune system mice in CAR‐T therapy—Application evaluation and improvement

Yue,

Bai

2023

Anim Models and Exp Med

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In recent years, humanized immune system (HIS) mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields, better mimicking the human immune system and the tumor immune microenvironment, compared to traditional immunodeficient mice. To better promote the application of HIS mice in preclinical research, we selectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor (CAR) ‐T cells in various antiviral and antitumor treatments. By exploring its application in preclinical research, we find that it can better reflect the actual clinical patient condition, with the advantages of providing high‐efficiency detection indicators, even for progressive research and development. We believe that it has better clinical patient simulation and promotion for the updated design of CAR‐T cell therapy than directly transplanted immunodeficient mice. The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction, combining multiple models, and unifying sources and organoid substitution. Strategy study of relapse and toxicity after CAR‐T treatment also provides more possibilities for application and development.

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“…Humanized mouse models with a functional human immune system (HIS) have been widely used to study human immunity and immune‐relevant complications 1 . Although high levels of human lymphohematopoietic chimerism can be readily achieved in immunodeficient mice by transplanting human CD34 + hematopoietic stem/progenitor cells, 2,3 HIS mice generally show poor human natural killer (NK) and myeloid cell reconstitution and limited B‐cell maturation, primarily because of the lack of sufficient cross‐reactivity between mouse cytokines and human cells 4–7 .…”

Section: Introductionmentioning

confidence: 99%

“…Humanized mouse models with a functional human immune system (HIS) have been widely used to study human immunity and immune-relevant complications. 1 Although high levels of human lymphohematopoietic chimerism can be readily achieved in immunodeficient mice by transplanting human CD34 + hematopoietic stem/ progenitor cells, 2,3 HIS mice generally show poor human natural killer (NK) and myeloid cell reconstitution and limited B-cell maturation, primarily because of the lack of sufficient cross-reactivity between mouse cytokines and human cells. [4][5][6][7] For example, low amino acid sequence similarity between mouse and human granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, stem cell factor (SCF), IL-6, IL-15 and thrombopoietin lead to poor human cell responses to these proteins, and consequently compromise human myeloid, NK and B-cell differentiation and function.…”

Section: Introductionmentioning

confidence: 99%

Improvement of human myeloid and natural killer cell development in humanized mice via hydrodynamic injection of transposon plasmids containing multiple human cytokine genes

et al. 2022

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Humanized mice reconstituted with a functional human immune system (HIS) are instrumental in studying human immunity and immune disorders in vivo. The poor or lack of cross-reactivity between mouse cytokines and human cells limits the development and/or function of human immune cell subsets including human myeloid, natural killer and B cells. Here we explored the potential to achieve long-term production of human cytokines in immunodeficient mice using a transposon-plasmid-based hydrodynamic injection approach. We constructed a transposon-plasmid carrying five human cytokine coding sequences (named PB-5F), and observed that four of the cytokines (granulocyte-macrophage colony-stimulating factor, interleukin (IL)-15, IL-6 and IL-3) were detectable in sera and three (granulocytemacrophage colony-stimulating factor, IL-15 and IL-6) showed long-term production in immunodeficient mice that received a single hydrodynamic injection of PB-5F plus the transposase plasmid (Super PB). Furthermore, a single injection of PB-5F/Super PB markedly enhanced the reconstitution of human myeloid cells and natural killer cells, and promoted human B-cell maturation in HIS mice. Taken together, our data revealed that hydrodynamic injection of the PB-5F/Super PB vectors may serve as a convenient and efficacious means to promote human immune function in HIS mice.

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Human Immune System Mice With Autologous Tumor for Modeling Cancer Immunotherapies

Cited by 6 publications

References 66 publications

Humanized mouse models for immuno-oncology research

Humanized mouse models for immuno-oncology research

Progress, implications, and challenges in using humanized immune system mice in CAR‐T therapy—Application evaluation and improvement

Improvement of human myeloid and natural killer cell development in humanized mice via hydrodynamic injection of transposon plasmids containing multiple human cytokine genes

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