Methods for Studying Mouse and Human Invariant Natural Killer T Cells

Zhou, Yang; Li, Yan-Ruide; Zeng, Samuel; Yang, Lili

doi:10.1007/978-1-0716-1775-5_4

Cited by 10 publications

(11 citation statements)

References 19 publications

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“…Furthermore, in hematological and solid tumor models, adoptive transfer of iNKT cells reduces tumor burden and enhances overall survival ( Fujii et al., 2013 ). Our previous studies have demonstrated the antitumor functions of HSC-iNKT cells in vivo when targeting CD1d positive and negative cancer cells ( Li et al., 2021b ; Zhou et al., 2021 ). Importantly, HSC-iNKT cells do not recognize mismatched MHCs and thus pose no risk of inducing GvHD; furthermore, because of their intrinsic low expression of HLA-I and II molecules, these cells are resistant to allorejection ( Li et al., 2021b , 2022b ).…”

Section: Discussionmentioning

confidence: 99%

Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers

Li¹,

Zeng²,

Dunn³

et al. 2022

iScience

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Section: Discussionmentioning

confidence: 99%

Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers

Li¹,

Zeng²,

Dunn³

et al. 2022

iScience

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“…PBMCs were MACS-sorted via anti-iNKT microbead (Miltenyi Biotech) labeling to enrich iNKT cells [ 48 ]. Cells were then stimulated with donor-matched irradiated αGC-PBMCs at a ratio of 1:1 and cultured in the C10 medium supplemented with human IL-7 (10 ng/mL) and IL-15 (10 ng/mL) for 2–3 weeks.…”

Section: Methodsmentioning

confidence: 99%

Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Zhou

Wilson

et al. 2022

IJMS

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Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision.

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“…Since stem cells possess unique properties for creating allogeneic cell therapies, using stem cell-derived iNKT cells or CAR-iNKT cells is an active area research. The Yang, Kaneko, and Taniguchi groups have reported the successful production of human iNKT cells by the genetic engineering of HSCs or differentiation iPSCs, and the iNKT cells were responsive to a-Galcer stimulation and executed potent anti-tumor capability toward leukemia, multiple myeloma, and solid tumors [ 9 , 49 , 64 , 65 , 88 , 120 ]. These pre-clinical results provide promising support for the development of iNKT cells as allogeneic third-party universal donors to change the paradigm of cancer immunotherapy.…”

Section: Allogeneic Stem Cell-engineered Unconventional T Cell-based Therapymentioning

confidence: 99%

“…Autologous iNKT cell therapies face the same challenges as autologous conventional αβ T cell therapy, with an additional hurdle mounted by the rarity of iNKT cells, which account for about less than 1% of peripheral blood mononuclear cells [ 62 , 63 , 64 , 65 ]. γδ T cells, although to a lesser extent, are also scarce in the periphery (5% of PBMCs) [ 66 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Stem Cell-Derived Immune Cells for Off-the-Shelf Cancer Immunotherapies

Dunn

Zhou

et al. 2021

Cells

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Cell-based cancer immunotherapy has revolutionized the treatment of hematological malignancies. Specifically, autologous chimeric antigen receptor-engineered T (CAR-T) cell therapies have received approvals for treating leukemias, lymphomas, and multiple myeloma following unprecedented clinical response rates. A critical barrier to the widespread usage of current CAR-T cell products is their autologous nature, which renders these cellular products patient-selective, costly, and challenging to manufacture. Allogeneic cell products can be scalable and readily administrable but face critical concerns of graft-versus-host disease (GvHD), a life-threatening adverse event in which therapeutic cells attack host tissues, and allorejection, in which host immune cells eliminate therapeutic cells, thereby limiting their antitumor efficacy. In this review, we discuss recent advances in developing stem cell-engineered allogeneic cell therapies that aim to overcome the limitations of current autologous and allogeneic cell therapies, with a special focus on stem cell-engineered conventional αβ T cells, unconventional T (iNKT, MAIT, and γδ T) cells, and natural killer (NK) cells.

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Methods for Studying Mouse and Human Invariant Natural Killer T Cells

Cited by 10 publications

References 19 publications

Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers

Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers

Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors

Development of Stem Cell-Derived Immune Cells for Off-the-Shelf Cancer Immunotherapies

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