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Artikel ; Online: Into the multiverse of gene edited NK cell-based therapeutic strategies.

Goldenson, Benjamin H / Kaufman, Dan S

2021 Band 28, Heft 12, Seite(n) 2041–2043

Abstract: In this issue of Cell Stem Cell, Woan et al., (2021) investigate the anti-cancer activity of triple gene edited iPSC-derived natural killer (NK) cells and demonstrate that expression of a modified CD16a and interleukin (IL)-15 receptor combined with ... ...

Abstract	In this issue of Cell Stem Cell, Woan et al., (2021) investigate the anti-cancer activity of triple gene edited iPSC-derived natural killer (NK) cells and demonstrate that expression of a modified CD16a and interleukin (IL)-15 receptor combined with knockout of CD38 improves NK cell-mediated activity against leukemia and multiple myeloma.
Mesh-Begriff(e)	Cell Line, Tumor ; Gene Editing ; Humans ; Induced Pluripotent Stem Cells ; Killer Cells, Natural ; Multiple Myeloma/genetics ; Multiple Myeloma/therapy
Sprache	Englisch
Erscheinungsdatum	2021-12-10
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2021.11.004
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting.

Goldenson, Benjamin H / Hor, Pooja / Kaufman, Dan S

Frontiers in immunology

2022 Band 13, Seite(n) 841107

Abstract: Treatment of cancer with allogeneic natural killer (NK) cell therapies has seen rapid development, especially use against hematologic malignancies. Clinical trials of NK cell-based adoptive transfer to treat relapsed or refractory malignancies have used ... ...

Abstract	Treatment of cancer with allogeneic natural killer (NK) cell therapies has seen rapid development, especially use against hematologic malignancies. Clinical trials of NK cell-based adoptive transfer to treat relapsed or refractory malignancies have used peripheral blood, umbilical cord blood and pluripotent stem cell-derived NK cells, with each approach undergoing continued clinical development. Improving the potency of these therapies relies on genetic modifications to improve tumor targeting and to enhance expansion and persistence of the NK cells. Induced pluripotent stem cell (iPSC)-derived NK cells allow for routine targeted introduction of genetic modifications and expansion of the resulting NK cells derived from a clonal starting cell population. In this review, we discuss and summarize recent important advances in the development of new iPSC-derived NK cell therapies, with a focus on improved targeting of cancer. We then discuss improvements in methods to expand iPSC-derived NK cells and how persistence of iPSC-NK cells can be enhanced. Finally, we describe how these advances may combine in future NK cell-based therapy products for the treatment of both hematologic malignancies and solid tumors.
Mesh-Begriff(e)	Animals ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/therapy ; Humans ; Immunotherapy, Adoptive/methods ; Induced Pluripotent Stem Cells/cytology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism
Chemische Substanzen	Receptors, Chimeric Antigen
Sprache	Englisch
Erscheinungsdatum	2022-02-03
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.841107
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Engineered human pluripotent stem cell-derived natural killer cells: the next frontier for cancer immunotherapy.

Zhu, Huang / Kaufman, Dan S

Blood science (Baltimore, Md.)

2019 Band 1, Heft 1, Seite(n) 4–11

Abstract: Adoptive immunotherapy using immune effector cells has revolutionized cancer treatments with approval of two autologous chimeric antigen receptor (CAR) T cell therapies by the US FDA. Clinical trials using natural killer (NK) cell-based adoptive ... ...

Abstract	Adoptive immunotherapy using immune effector cells has revolutionized cancer treatments with approval of two autologous chimeric antigen receptor (CAR) T cell therapies by the US FDA. Clinical trials using natural killer (NK) cell-based adoptive immunotherapy have been shown to be safe and effective for treatment of multiple malignancies, especially acute myelogenous leukemia. However, most of these trails use primary NK cells isolated from peripheral or cord blood which can have donor-dependent variability and can be challenging to genetic engineer to improve antitumor functions, limiting the widespread use of this promising new therapy. NK cells can now be routinely produced from human pluripotent stem cells, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). These pluripotent stem cells are homogenous, easy to genetically modify on a clonal level and can be used as unlimited source of NK cells, making them ideal population to develop standardized, off-the-shelf adoptive NK cell therapy products. In this review, we discuss recent advances of obtaining and expanding hESC and iPSC-derived NK cells and novel genetic engineering strategies that are being applied to improve their antitumor functions.
Sprache	Englisch
Erscheinungsdatum	2019-09-17
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ISSN	2543-6368
ISSN (online)	2543-6368
DOI	10.1097/BS9.0000000000000023
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: An Improved Method to Produce Clinical-Scale Natural Killer Cells from Human Pluripotent Stem Cells.

Zhu, Huang / Kaufman, Dan S

Methods in molecular biology (Clifton, N.J.)

2019 Band 2048, Seite(n) 107–119

Abstract: Human natural killer (NK) cell-based adoptive anticancer immunotherapy has gained intense interest with many clinical trials actively recruiting patients to treat a variety of both hematological malignancies and solid tumors. Most of these trials use ... ...

Abstract	Human natural killer (NK) cell-based adoptive anticancer immunotherapy has gained intense interest with many clinical trials actively recruiting patients to treat a variety of both hematological malignancies and solid tumors. Most of these trials use primary NK cells isolated either from peripheral blood (PB-NK cells) or umbilical cord blood (UCB-NK cells), though these sources require NK cell collection for each patient leading to donor variability and heterogeneity in the NK cell populations. In contrast, NK cells derived human embryonic stem cells (hESC-NK cells) or induced pluripotent stem cells (hiPSC-NK cells) provide more homogeneous cell populations that can be grown at clinical scale, and genetically engineered if needed. These characteristics make hESC-/iPSC-derived NK cells an ideal cell population for developing standardized, "off-the-shelf" immunotherapy products. Additionally, production of NK cells from undifferentiated human pluripotent stem cells enables studies to better define pathways that regulate human NK cell development and function. Our group previously has established a stromal-free, two-stage culture system to derive NK cells from hESC/hiPSC in vitro followed by clinical-scale expansion of these cells using interleukin (IL)-21 expressing artificial antigen-presenting cells. However, prior to differentiation, this method requires single-cell adaptation of hESCs/hiPSCs which takes months. Recently we optimized this method by adapting the mouse embryonic fibroblast-dependent hESC/hiPSC to feeder-free culture conditions. These feeder-free hESCs/hiPSCs are directly used to form embryoid body (EB) to generate hemato-endothelial precursor cells. This new method produces mature, functional NK cells with higher efficiency to enable rapid production of an essentially unlimited number of homogenous NK cells that can be used for standardized, targeted immunotherapy for the treatment of refractory cancers and infectious diseases.
Mesh-Begriff(e)	Animals ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Culture Media/metabolism ; Embryoid Bodies/physiology ; Flow Cytometry/instrumentation ; Flow Cytometry/methods ; Human Embryonic Stem Cells/physiology ; Humans ; Immunotherapy, Adoptive/methods ; Induced Pluripotent Stem Cells/physiology ; Killer Cells, Natural/physiology ; Killer Cells, Natural/transplantation ; Mice ; Neoplasms/immunology ; Neoplasms/therapy
Chemische Substanzen	Culture Media
Sprache	Englisch
Erscheinungsdatum	2019-08-08
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9728-2_12
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: iPSC-derived engineered T cells, NK cells, macrophages and DCs in immunotherapy

Xue, Dixuan / Lu, Shan / Zhang, Hailing / Zhang, Li / Dai, Zhijun / Kaufman, Dan S. / Zhang, Jin

Trends in Biotechnology.

2023

Abstract: T cells, natural killer (NK) cells, macrophages (Macs) and dendritic cells (DCs) are among the most common sources for immune cell-based therapies for cancer. Antitumor activity can be enhanced in iPSC-derived immune cells by using iPSCs as a platform ... ...

Abstract	T cells, natural killer (NK) cells, macrophages (Macs) and dendritic cells (DCs) are among the most common sources for immune cell-based therapies for cancer. Antitumor activity can be enhanced in iPSC-derived immune cells by using iPSCs as a platform for stable genetic modifications that impact immune-activating or suppressive signaling pathways, such as transducing a chimeric antigen receptor (CAR) or deletion of immunosuppressive checkpoint molecules. This review will outline the utility of four iPSC-derived immune cell-based therapies, highlight the latest progress and future trend in the genome editing strategies designed to improve efficacy, safety and universality, and provide perspectives that compare different contexts in which each of these iPSC-derived immune cell types can be most effectively employed.
Schlagwörter	antigens ; antineoplastic activity ; biotechnology ; genome ; immunosuppression ; immunotherapy ; macrophages ; Induced pluripotent stem cells (iPSCs) ; Cancer immunotherapy ; T cells ; NK cells ; Dendritic cells ; Gene/Cell engineering ; genome editing
Sprache	Englisch
Erscheinungsort	Elsevier Ltd
Dokumenttyp	Artikel ; Online
Anmerkung	Pre-press version
ZDB-ID	47474-5
ISSN	1879-3096 ; 0167-7799
ISSN (online)	1879-3096
ISSN	0167-7799
DOI	10.1016/j.tibtech.2023.02.003
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Advances in the role of the aryl hydrocarbon receptor to regulate early hematopoietic development.

Angelos, Mathew G / Kaufman, Dan S

Current opinion in hematology

2018 Band 25, Heft 4, Seite(n) 273–278

Abstract: Purpose of review: We summarize current advances to define the role the aryl hydrocarbon receptor (AHR) plays in mammalian hematopoiesis. We emphasize approaches to modulate AHR throughout human hematopoietic development in vitro to support the ... ...

Abstract	Purpose of review: We summarize current advances to define the role the aryl hydrocarbon receptor (AHR) plays in mammalian hematopoiesis. We emphasize approaches to modulate AHR throughout human hematopoietic development in vitro to support the production of clinically relevant blood products suitable for patient care. Recent findings: Initial data demonstrate that both pharmacologic AHR inhibition and genetic deletion from human pluripotent stem cells provide useful strategies to enhance the yield of hematopoietic stem and progenitor cells. AHR hyperactivation following the induction of CD34 megakaryocyte-erythroid progenitors skews developed toward erythroid lineages, whereas AHR inhibition supports platelet production. At the level of lymphoid specification, AHR inhibition enhances the proliferation and differentiation of functional human natural killer cells, whereas hyperactivation leads to production of Group 3 innate lymphoid cells and provides a novel platform for studying human innate lymphoid cell development. Summary: Modulation of AHR in human hematopoietic cells in vitro is a promising tool to mediate development of terminal hematopoietic cell populations with significant clinical implications to generate cells suitable for antitumor immunotherapy and bone marrow transplantation.
Mesh-Begriff(e)	Animals ; Cell Differentiation ; Cell Proliferation ; Hematopoiesis ; Hematopoietic Stem Cells/metabolism ; Humans ; Pluripotent Stem Cells/metabolism ; Receptors, Aryl Hydrocarbon/antagonists & inhibitors ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism
Chemische Substanzen	Receptors, Aryl Hydrocarbon
Sprache	Englisch
Erscheinungsdatum	2018-04-26
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000432
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Tu-mor(e) blood cells from human pluripotent stem cells.

Kaufman, Dan S

Blood

2013 Band 121, Heft 8, Seite(n) 1245–1246

Abstract: Studies by Amabile et al reported in this issue of Blood use a novel strategy of teratoma formation from human induced pluripotent stem cells (iPSCs) to isolate hematopoietic stem/progenitor cells (HSPCs) capable of in vivo engraftment and producing ... ...

Abstract	Studies by Amabile et al reported in this issue of Blood use a novel strategy of teratoma formation from human induced pluripotent stem cells (iPSCs) to isolate hematopoietic stem/progenitor cells (HSPCs) capable of in vivo engraftment and producing functional lymphocytes.(1)
Mesh-Begriff(e)	Animals ; Hematopoiesis/physiology ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/cytology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Teratoma/pathology
Sprache	Englisch
Erscheinungsdatum	2013-02-20
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2013-01-472563
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Induced pluripotent stem cell-derived engineered T cells, natural killer cells, macrophages, and dendritic cells in immunotherapy.

Xue, Dixuan / Lu, Shan / Zhang, Hailing / Zhang, Li / Dai, Zhijun / Kaufman, Dan S / Zhang, Jin

Trends in biotechnology

2023 Band 41, Heft 7, Seite(n) 907–922

Abstract: T cells, natural killer (NK) cells, macrophages (Macs), and dendritic cells (DCs) are among the most common sources for immune-cell-based therapies for cancer. Antitumor activity can be enhanced in induced pluripotent stem cell (iPSC)-derived immune ... ...

Abstract	T cells, natural killer (NK) cells, macrophages (Macs), and dendritic cells (DCs) are among the most common sources for immune-cell-based therapies for cancer. Antitumor activity can be enhanced in induced pluripotent stem cell (iPSC)-derived immune cells by using iPSCs as a platform for stable genetic modifications that impact immuno-activating or -suppressive signaling pathways, such as transducing a chimeric antigen receptor (CAR) or deletion of immunosuppressive checkpoint molecules. This review outlines the utility of four iPSC-derived immune-cell-based therapies, highlight the latest progress and future trends in the genome-editing strategies designed to improve efficacy, safety, and universality, and provides perspectives that compare different contexts in which each of these iPSC-derived immune cell types can be most effectively used.
Mesh-Begriff(e)	Humans ; Induced Pluripotent Stem Cells/metabolism ; Natural Killer T-Cells/metabolism ; Immunotherapy ; Macrophages ; Neoplasms ; Dendritic Cells ; Immunotherapy, Adoptive
Sprache	Englisch
Erscheinungsdatum	2023-02-28
Erscheinungsland	England
Dokumenttyp	Journal Article ; Review
ZDB-ID	47474-5
ISSN	1879-3096 ; 0167-7799
ISSN (online)	1879-3096
ISSN	0167-7799
DOI	10.1016/j.tibtech.2023.02.003
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Development of innate immune cells from human pluripotent stem cells.

Bernareggi, Davide / Pouyanfard, Somayeh / Kaufman, Dan S

Experimental hematology

2019 Band 71, Seite(n) 13–23

Abstract: Mouse and human pluripotent stem cells have been widely used to study the development of the hematopoietic and immune systems. Although not all cells can be derived with the same efficiency, immune cells such as natural killer (NK) cells and macrophages ... ...

Abstract	Mouse and human pluripotent stem cells have been widely used to study the development of the hematopoietic and immune systems. Although not all cells can be derived with the same efficiency, immune cells such as natural killer (NK) cells and macrophages can be easily produced from PSCs to enable development of new cell-based therapies. NK cells and macrophages are part of the innate immune system, the first line of defense against malignancies and infectious disease. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived NK cells can be produced at a clinical scale suitable for translation into clinical trials. Additionally, PSCs can be genetically modified to produce hESC/iPSC-derived human NK cells with enhanced antitumor activity. These engineered NK cells can express a stabilized version of the high-affinity Fc receptor CD16, chimeric antigen receptors, or other strategies to enable more potent and targeted cellular immunotherapies. Moreover, macrophages can also be routinely and efficiently produced from hESCs and iPSCs as a tool to expand our knowledge of the basic biology of these cells. hESC- and iPSC-derived macrophages can also be employed as a novel approach for cancer immunotherapy, as well as a strategy to repair or regenerate diseased and damaged tissues and organs.
Mesh-Begriff(e)	Animals ; Cell Differentiation/immunology ; Humans ; Immune System/cytology ; Immune System/immunology ; Immune System/metabolism ; Immunity, Innate ; Immunotherapy, Adoptive ; Killer Cells, Natural/cytology ; Killer Cells, Natural/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/therapy ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism
Sprache	Englisch
Erscheinungsdatum	2019-01-04
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	185107-x
ISSN	1873-2399 ; 0531-5573 ; 0301-472X
ISSN (online)	1873-2399
ISSN	0531-5573 ; 0301-472X
DOI	10.1016/j.exphem.2018.12.005
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: CHMP2A regulates broad immune cell-mediated antitumor activity in an immunocompetent in vivo head and neck squamous cell carcinoma model.

Yun, Jiyoung / Saddawi-Konefka, Robert / Goldenson, Benjamin / Al-Msari, Riyam / Bernareggi, Davide / Thangaraj, Jaya L / Tang, Shiqi / Patel, Sonam H / Luna, Sarah M / Gutkind, J Silvio / Kaufman, Dan

Journal for immunotherapy of cancer

2024 Band 12, Heft 5

Abstract: Background: Natural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define ... ...

Abstract	Background: Natural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity. In previous studies from our group, a genome-wide CRISPR-Cas9 screen identified Charged Multivesicular Body Protein 2A ( Methods: Here, we use an immunocompetent mouse model to demonstrate that CHMP2A serves as a targetable regulator of not only NK cell-mediated immunity but also other immune cell populations. Using the recently characterized murine 4MOSC model system, a syngeneic, tobacco-signature murine head and neck squamous cell carcinoma model, we deleted mCHMP2A using CRISPR/Cas9-mediated knock-out (KO), following orthotopic transplantation into immunocompetent hosts. Results: We found that mCHMP2A KO in 4MOSC1 cells leads to more potent NK-mediated tumor cell killing in vitro in these tumor cells. Moreover, following orthotopic transplantation, KO of mCHMP2A in 4MOSC1 cells, but not the more immune-resistant 4MOSC2 cells enables both T cells and NK cells to better mediate antitumor activity compared with wild type (WT) tumors. However, there was no difference in tumor development between WT and mCHMP2A KO 4MOSC1 or 4MOSC2 tumors when implanted in immunodeficient mice. Mechanistically, we find that mCHMP2A KO 4MOSC1 tumors transplanted into the immunocompetent mice had significantly increased CD4 Conclusions: Together, these studies demonstrate that CHMP2A is a targetable inhibitor of cellular antitumor immunity.
Mesh-Begriff(e)	Animals ; Humans ; Mice ; Cell Line, Tumor ; Disease Models, Animal ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/genetics ; Immunocompetence ; Killer Cells, Natural/immunology ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/genetics
Chemische Substanzen	Chmp2a protein, mouse
Sprache	Englisch
Erscheinungsdatum	2024-05-03
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-007187
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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