EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity

Jing, Ran; Scarfò, Irene; Najia, Mohamad Ali; Rocha, Edroaldo Lummertz da; Han, A-Reum; Sanborn, Michael; Bingham, Trevor; Kubaczka, Caroline; Jha, Deepak Kumar; Falchetti, Marcelo; Schlaeger, Thorsten M.; North, Trista E.; Maus, Marcela V.; Daley, George Q.

doi:10.1016/j.stem.2022.06.014

Cited by 44 publications

(45 citation statements)

References 92 publications

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“…γδ T cells possess beneficial properties of both T and NK cells. Since CAR-T and CAR-NK cells are used in patients with cancer ( 5 , 6 ), many trials have reported the generation of tumor-targeted human lymphocytes from PSCs with diverse CAR loading ( 25 - 27 ). However, the major drawback of CAR-T production was the limitation that the TCR repertoire rearrangement is unpredictable and only allows loaded target molecules because the TCR rearranges randomly upon differentiation of PSC-derived CAR-T or NK cells in vitro .…”

Section: Discussionmentioning

confidence: 99%

Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

et al. 2022

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γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

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Section: Discussionmentioning

confidence: 99%

Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

et al. 2022

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“…This study showed that NK cells derived from iPSCs display potent tumour-specific cytotoxic activity in NSG mice and promote T cell infiltration of tumours in Hu-PBL-SCID models. The use of iPSCs derived from patients with cancer to generate human immune cells and haematopoietic stem and progenitor cells (HSPCs) could provide unlimited quantities of these cell populations for engraftment into humanized mice bearing autologous tumours as well as novel platforms for the testing of new therapies 93,94 .…”

Section: Review Articlementioning

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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“…This novel CAR-derived T-cell circumvention of donor-derived defects will greatly promote the promotion of CAR-T therapy. 435 With the continuous maturation and application of the coculture system of immune cells and organoids, it is believed that the organoid model will be a major asset to the field of immunotherapy.…”

Section: Digestive System Organoid Models and Precision And Personali...mentioning

confidence: 99%

Applications of human organoids in the personalized treatment for digestive diseases

Wang

Guo

Jin

et al. 2022

Sig Transduct Target Ther

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Digestive system diseases arise primarily through the interplay of genetic and environmental influences; there is an urgent need in elucidating the pathogenic mechanisms of these diseases and deploy personalized treatments. Traditional and long-established model systems rarely reproduce either tissue complexity or human physiology faithfully; these shortcomings underscore the need for better models. Organoids represent a promising research model, helping us gain a more profound understanding of the digestive organs; this model can also be used to provide patients with precise and individualized treatment and to build rapid in vitro test models for drug screening or gene/cell therapy, linking basic research with clinical treatment. Over the past few decades, the use of organoids has led to an advanced understanding of the composition of each digestive organ and has facilitated disease modeling, chemotherapy dose prediction, CRISPR-Cas9 genetic intervention, high-throughput drug screening, and identification of SARS-CoV-2 targets, pathogenic infection. However, the existing organoids of the digestive system mainly include the epithelial system. In order to reveal the pathogenic mechanism of digestive diseases, it is necessary to establish a completer and more physiological organoid model. Combining organoids and advanced techniques to test individualized treatments of different formulations is a promising approach that requires further exploration. This review highlights the advancements in the field of organoid technology from the perspectives of disease modeling and personalized therapy.

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EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity

Cited by 44 publications

References 92 publications

Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

Humanized mouse models for immuno-oncology research

Applications of human organoids in the personalized treatment for digestive diseases

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