In vivo generation of CAR T cells in the presence of human myeloid cells

Ho, Naphang; Agarwal, Shiwani; Milani, Michela; Cantore, Alessio; Buchholz, Christian J.; Thalheimer, Frederic B.

doi:10.1016/j.omtm.2022.06.004

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…D. Targeting T cells in vivo and delivering micro-RNA (miRNA) that stabilizes T reg mediated-self-tolerance restores effector/regulatory T cells balance for autoimmune diseases treatment [34]. E. CAR T cells are engineered in vivo through targeted delivery of mRNA [40] or viral RNA [46,48,66] for transient or durable CAR expression respectively.…”

Section: Discussionmentioning

confidence: 99%

In vivo gene delivery to immune cells

Siebart,

Chan,

Yao

et al. 2024

Current Opinion in Biotechnology

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Section: Discussionmentioning

confidence: 99%

In vivo gene delivery to immune cells

Siebart,

Chan,

Yao

et al. 2024

Current Opinion in Biotechnology

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“…Individual immune cell subsets, including T cells and NK cells, are isolated, engineered to express a CAR and then injected into tumour-bearing immunodeficient mice 25 . In the past few years, technological developments have enabled the isolation of human immune cells (including T, NK and myeloid cells) from CD34 + HSPC-engrafted mice for transduction of CAR constructs [232][233][234] . Given that both CD4 + and CD8 + T cells are the dominant CD45 + subset in Hu-PBL mice, immunotherapies exploiting human T cells can be effectively tested in these models, although human CD4 + T reg cells are generally not abundant after PBMC engraftment 54 .…”

Section: Engraftment Strategy and Immune Cells Of Interestmentioning

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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“…Compared with the common humanized NSG (huNSG) model, which is generated by transgenic expression of stem cell factor (SCF), GM‐CSF, and IL‐3, NSG‐SGM3 mice reconstituted with human stem cells (huSGM3 mice) develop elevated numbers of human myeloid cells [ 102 ] and thus more closely mimic the human immune cell composition, and this mouse strain has been utilized to generate preclinical CAR‐T therapy‐associated CRS and neurotoxicity models. [ 103 ] To investigate the in vivo generation of CAR‐Ts in the presence of human myeloid cells, this group also evaluated the huSGM3 mouse model for in vivo CAR‐T induction with CD4‐LVs and CD8‐LVs, [ 104 ] and they showed that in vivo CAR‐T generation in mice with an intricate humanized immune system was less efficient than that in the huNSG model above reported owing to nonspecific phagocytosis of LVs by macrophages. As such, and given that phagocytosis could be prevented by producing LVs in cells lacking MHC‐I and overexpressing CD47, [ 105 ] the team produced shielded CD4‐LV sh and CD8‐LV sh particles in an optimized packing cell line, β2M −/− CD47 high HEK293T cells; these phagocytosis‐shielded targeted LVs achieved greatly improved in vivo transduction.…”

Section: Off‐the‐shelf Car‐based Agentsmentioning

confidence: 99%

Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies

Chen,

Hu,

Mei

2023

Advanced Science

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Chimeric antigen receptor T‐cell (CAR‐T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR‐T to CAR‐natural killer cell (CAR‐NK), CAR‐cytokine‐induced killer cell (CAR‐CIK), and CAR‐macrophage (CAR‐MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR‐engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR‐engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon.

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In vivo generation of CAR T cells in the presence of human myeloid cells

Cited by 11 publications

References 36 publications

In vivo gene delivery to immune cells

In vivo gene delivery to immune cells

Humanized mouse models for immuno-oncology research

Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies

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