iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting

Goldenson, Benjamin; Hor, Pooja; Kaufman, Dan S.

doi:10.3389/fimmu.2022.841107

Cited by 60 publications

(33 citation statements)

References 153 publications

(201 reference statements)

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“…PB-derived NK cells can be easily provided, and require activation and expansion, but the yield could be affected by donor variability. IPSCs can be maintained in an undifferentiated state and grown indefinitely, therefore enabling the production of huge numbers of homogeneous NK cells providing a base for a standardized, off-the-shelf approach [ 123 , 124 , 125 ].…”

Section: Adoptive Transfer Of Nk Cellsmentioning

confidence: 99%

NK Cell-Based Immunotherapy in Colorectal Cancer

et al. 2022

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Human Natural Killer (NK) cells are all round players in immunity thanks to their powerful and immediate response against transformed cells and the ability to modulate the subsequent adaptive immune response. The potential of immunotherapies based on NK cell involvement has been initially revealed in the hematological setting but has inspired the design of different immune tools to also be applied against solid tumors, including colorectal cancer (CRC). Indeed, despite cancer prevention screening plans, surgery, and chemotherapy strategies, CRC is one of the most widespread cancers and with the highest mortality rate. Therefore, further efficient and complementary immune-based therapies are in urgent need. In this review, we gathered the most recent advances in NK cell-based immunotherapies aimed at fighting CRC, in particular, the use of monoclonal antibodies targeting tumor-associated antigens (TAAs), immune checkpoint blockade, and adoptive NK cell therapy, including NK cells modified with chimeric antigen receptor (CAR-NK).

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Section: Adoptive Transfer Of Nk Cellsmentioning

confidence: 99%

NK Cell-Based Immunotherapy in Colorectal Cancer

et al. 2022

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“…UCB can also be a source of human iPSCs, which represent an alternative to produce NK cells in a standardized manner for anticancer immunotherapy [ 157 ]. Indeed, iPSCs can be obtained through the genetic reprogramming of various somatic cell types by induced overexpression of different stemness transcription factors, usually represented by Oct, Sox2, Klf4, and c-Myc [ 158 ].…”

Section: The Challenge Of Designing Ucb-derived Nk Cell Adoptive Therapymentioning

confidence: 99%

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Damele

Spaggiari

Parodi

et al. 2022

Cancers

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In the last 20 years, Natural Killer (NK) cell-based immunotherapy has become a promising approach to target various types of cancer. Indeed, NK cells play a pivotal role in the first-line defense against tumors through major histocompatibility complex-independent immunosurveillance. Their role in the control of leukemia relapse has been clearly established and, moreover, the presence of NK cells in the tumor microenvironment (TME) generally correlates with good prognosis. However, it has also been observed that, often, NK cells poorly infiltrate the tumor tissue, and, in TME, their functions may be compromised by immunosuppressive factors that contribute to the failure of anti-cancer immune response. Currently, studies are focused on the design of effective strategies to expand NK cells and enhance their cytotoxic activity, exploiting different cell sources, such as peripheral blood (PB), umbilical cord blood (UCB) and NK cell lines. Among them, UCB represents an important source of mature NK cells and CD34+ Hematopoietic Stem and Progenitor Cells (HSPCs), as precursors of NK cells. In this review, we summarize the UCB-derived NK cell activity in the tumor context, review the different in-vitro models to expand NK cells from UCB, and discuss the importance of their exploitation in anti-tumor immunotherapy protocols.

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“…The irradiation limits their ability to expand and persist in vivo, reducing antitumor efficacy [ 92 ]. Preclinical studies and clinical trials of cell therapy have shown that improved CAR-T cell persistence leads to better therapeutic efficacy [ 93 , 94 ]. Similar studies on NK cells have also shown that persistence in preclinical in vivo models correlates with better tumor killing ability [ 67 ].…”

Section: Source and Preparation Of Nk Or Car-nk Cells For Clinical Usementioning

confidence: 99%

Current Progress of CAR-NK Therapy in Cancer Treatment

Pang

Wang

et al. 2022

Cancers

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CD8+ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing cancer cells. The success of CAR-T therapy in the treatment of acute lymphoblastic leukemia (ALL) and other types of blood cancers proved that the immunotherapy is an effective approach in fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) and cytokine release syndrome (CRS), cannot be ignored for the CAR-T therapy. CAR-NK therapy, then, has its advantage in lacking these adverse effects and works as effective as CAR-T in terms of killing. Despite these, NK cells are known to be hard to transduce, expand in vitro, and sustain shorter in vivo comparing to infiltrated T cells. Moreover, CAR-NK therapy faces challenges as CAR-T therapy does, e.g., the time, the cost, and the potential biohazard due to the use of animal-derived products. Thus, enormous efforts are needed to develop safe, effective, and large-scalable protocols for obtaining CAR-NK cells. Here, we reviewed current progress of CAR-NK therapy, including its biological properties, CAR compositions, preparation of CAR-NK cells, and clinical progresses. We also discussed safety issues raised from genetic engineering. We hope this review is instructive to the research community and a broad range of readers.

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iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting

Cited by 60 publications

References 153 publications

NK Cell-Based Immunotherapy in Colorectal Cancer

NK Cell-Based Immunotherapy in Colorectal Cancer

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Current Progress of CAR-NK Therapy in Cancer Treatment

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